Submissions for variant NM_000152.5(GAA):c.755dup (p.Pro253fs)

dbSNP: rs1555599619

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000669528	SCV001443305	pathogenic	Glycogen storage disease, type II	2020-07-20	reviewed by expert panel	curation	This variant, c.755dup (p.Pro253AlafsTer77), is a frameshift variant that is predicted to result in a premature termination codon, nonsense mediated decay, and lack of gene product, meeting PVS1. This variant is not in gnomAD v2.1.1, meeting PM2. One patient has been reported who meets the ClinGen LSD VCEP's specifications for PP4 and who is compound heterozygous for the variant and c.569G>A (p.Arg190His) (PMID 29124014). The phase is unknown. This is intrans data will be used in the assessment of p.Arg190His and is therefore not included here in order to avoid a circular argument. There is a ClinVar entry for this variant (Variation ID: 553981, one star review status) with one submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PP4.
Counsyl	RCV000669528	SCV000794288	likely pathogenic	Glycogen storage disease, type II	2017-10-05	criteria provided, single submitter	clinical testing