Variant database

Pompe disease GAA variant database

Variant database

Location	DNA nomenclature	RNA nomenclature	Protein nomenclature	Type of variant DNA	Type of variant RNA	Type of variant Protein	Predicted severity	ACMG classification	Phenotype with null allele	CRIM status	MAF	RS number	Biochemical evidence of pathogenicity	Splicing and translation prediction	Biochemical evidence of CRIM status	Prediction of CRIM status
GAA and part of CCDC40	Ch37/hg19:g.78,056,048_ 78,094,854delins14bp	r.(-212_*551del)	p.(0)	Deletion	Deletion	Deletion (whole gene)	Very severe	Pathogenic	Classic infantile	Negative	MAF not reported			no effect on splicing - deletion of whole GAA gene	deletion of whole GAA gene	protein is not expressed

CCDC40 and GAA exon 1	Ch37/hg19 chr17:78,059,821_ 78,076,592del	r.0	p.?	deletion	Deletion (intron variant)	No category	very severe	Pathogenic	Classic infantile	Unknown	MAF not reported			no effect on splicing	no expression found in allele specific PCR	protein is not expressed

exon 1A, 5' UTR	c.-338C>G	r.(-338c>g)	p.?	Substitution	Substitution	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs144639114		no effect on splicing		protein is expressed

exon 1A, 5' UTR	c.-260G>C	r.(-260g>c)	p.?	Substitution	Substitution	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs2304849		no effect on splicing		protein is expressed

exon 1A, 5' UTR	c.-178G>A	r.(-178g>a)	p.?	Substitution	Substitution	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs77514632		no effect on splicing		protein is expressed

intron 1A	c.-113+2T>C	r.spl	p.?	substitution	substitution/ splicing (splice donor site)	No category	Very severe	Pathogenic	Unknown (disease-associated)	Unknown	MAF not reported		affects splicing on exon 1 in minigene	loss of exon 1A splice donor site		unknown

exon 1B, 5' UTR	c.-82G>C	r.(-82g>c)	p.?	Substitution	Substitution	No category	Unknown	Uncertain significance	Unknown	Positive	MAF not reported			no effect on splicing		protein is expressed

exon 1B, 5' UTR	c.-75C>G	r.(-75c>g)	p.?	Substitution	Substitution	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs80020206		no effect on splicing		protein is expressed

intron 1B	c.-33+219G>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs4889961		no effect on splicing		protein is expressed

intron 1B	c.-33+316C>A	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs8077055		no effect on splicing		protein is expressed

intron 1B	c.-33+317C>T	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs8077056		no effect on splicing		protein is expressed

intron 1B	c.-33+671A>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs55751636		no effect on splicing		protein is expressed

intron 1B	c.-33+757G>A	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs28413147		no effect on splicing		protein is expressed

intron 1B	c.-33+903A>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs12450199		no effect on splicing		protein is expressed

intron 1B	c.-33+1104A>G	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs11150841		no effect on splicing		protein is expressed

intron 1B	c.-33+1172G>A	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs1442315		no effect on splicing		protein is expressed

intron 1B	c.-33+1190G>T	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs12602593		no effect on splicing		protein is expressed

intron 1B	c.-33+1309T>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs1442314		no effect on splicing		protein is expressed

intron 1B	c.-32-1298G>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs12602610		no effect on splicing		protein is expressed

intron 1B	c.-32-1124C>T	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs58959690		no effect on splicing		protein is expressed

intron 1B	c.-32-884T>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs145362066		no effect on splicing		protein is expressed

intron 1B	c.-32-793C>G	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs55666739		no effect on splicing		protein is expressed

intron 1B	c.-32-721G>C	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs75754966		generates a new cryptic splice accepter site		unknown

intron 1B	c.-32-686A>G	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs147264695		no effect on splicing		protein is expressed

intron 1B	c.-32-640C>T	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs12600845		no effect on splicing		protein is expressed

intron 1B	c.-32-521G>T	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs115060925		generates a new cyptic splice donor site		unknown

intron 1B	c.-32-494C>G	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs140325572		no effect on splicing		protein is expressed

intron 1B	c.-32-462G>A	r.(=)	p.?	Substitution	Substitution (intron variant)	No category	Non-pathogenic	Likely benign	Unknown	Positive	MAF is over 1%	rs74003606		no effect on splicing		protein is expressed

intron 1B	c.-32-17_-32-10delins(30)	r.?	p.?	Deletion/ insertion	deletion/ insertion (intron variant)	No category	very severe	Unknown significance	Classic infantile	Unknown	MAF not reported			N.D.		unknown

intron 1B	c.-32-13T>G	r.[=,-32_546del,-32_486del]	p.[=,0]	Substitution	Substitution/ Splicing (intron variant)	Deletion (translation initiation site)	Potentially mild	Pathogenic	Childhood or Adult	Positive	MAF is less than 1%	rs386834236	causes partial and complete skipping of exon 2	no effect on splicing	detection of leaky wildtype splicing	protein is expressed

intron 1B	c.-32-3C>G	r.(=)	p.?	Substitution	Substitution/ Splicing (intron variant)	No category	Less severe	Likely pathogenic	Unknown (disease-associated)	Unknown	MAF not reported			weakens exon 2 splice acceptor		unknown

intron 1B	c.-32-3C>A	r.(=)	p.?	Substitution	Substitution/ Splicing (intron variant)	No category	Less severe	Pathogenic	Childhood	Unknown	MAF not reported			weakens exon 2 splice acceptor		unknown

intron 1B	c.-32-2A>G	r.spl	p.?	Substitution	Substitution/ Splicing (splice acceptor site)	No category	Very severe	Pathogenic	Childhood or Adult	Unknown	MAF not reported			loss of exon 2 splice acceptor		unknown

intron 1B	c.-32-1G>C	r.spl	p.?	Substitution	Substitution/ Splicing (splice acceptor site)	No category	very severe	Pathogenic	Unknown (disease-associated)	Unknown	MAF not reported			loss of exon 2 splice acceptor and generation of a cryptic splice acceptor site		unknown

exon 2	c.1A>T	r.(1a>u)	p.(0)	Substitution	Substitution	Substitution (translation initiation codon)	Potentially less severe	Pathogenic	Unknown	Negative	MAF not reported		gives 0% residual activity in expression study	no effect on splicing - disrupts translation start codon		protein is not expressed

exon 2	c.1A>G	r.(1a>g)	p.(0)	Substitution	Substitution	Substitution (translation initiation codon)	Very severe	Pathogenic	Classic infantile or Childhood	Negative	MAF not reported		no protein on western blot	no effect on splicing - disrupts translation start codon	no endogeneous protein on western blot	protein is not expressed

exon 2	c.2T>C	r.(2u>c)	p.(0)	Substitution	Substitution	Substitution (translation initiation codon)	Potentially less severe	Likely pathogenic	Childhood	Negative	MAF not reported		gives 0% residual activity in expression study	no effect on splicing - disrupts translation start codon		protein is not expressed

exon 2	c.3G>A	r.(3g>a)	p.(0)	Substitution	Substitution	Substitution (translation initiation codon)	Very severe	Pathogenic	Classic infantile or Childhood	Negative	MAF not reported			new cryptic splice acceptor - disrupts translation start codon		protein is not expressed

exon 2	c.18_25del	r.(18_25del)	p.(Cys8Profs*24)	Deletion	Deletion	Frameshift	Very severe	Pathogenic	Classic infantile	Negative	MAF not reported			no effect on splicing - causes an out of frame product		protein is not expressed

exon 2	c.25del	r.(25del)	p.(Ser9Profs*34)	Deletion	Deletion	Frameshift	Very severe	Pathogenic	Unknown (disease-associated)	Negative	MAF not reported			no effect on splicing - causes an out of frame product		protein is not expressed

The Pompe disease GAA variant database represents an effort to collect all known variants in the GAA gene and is maintained and provide by the Pompe center, Erasmus MC.

We kindly ask you to reference one of the following articles if you use this database for research purposes:

de Faria, DOS, in 't Groen, SLM, Bergsma, AJ, et al. Update of the Pompe variant database for the prediction of clinical phenotypes: Novel disease-associated variants, common sequence variants, and results from newborn screening.
Human Mutation. 2021; 42: 119-134. https://doi.org/10.1002/humu.24148

Niño, MY, in 't Groen, SLM, Hoogeveen-Westerveld, M, et al. Extension of the Pompe mutation database by linking disease‐associated variants to clinical severity. Human Mutation. 2019; 40: 1954–1967. https://doi.org/10.1002/humu.23854

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Pompe disease GAA variant database