Submissions for variant NM_000152.5(GAA):c.1332T>C (p.Pro444=)

gnomAD frequency: 0.00015  dbSNP: rs200007324

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel	RCV000553536	SCV001371710	likely benign	Glycogen storage disease, type II	2023-03-13	reviewed by expert panel	curation	The NM_000152.5:c.1332T>C (p.Pro444=) variant in GAA is a synonymous (silent) variant that is not predicted to impact splicing; the nucleotide is not highly conserved (PhyloP 100 way score is -2.4 (BP4, BP7). There is a ClinVar entry for this variant (Variation ID: 286018). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BS1, BP4, BP7. (Classification approved by the ClinGen Lysosomal Diseases VCEP, March 13, 2023).
Eurofins Ntd Llc (ga)	RCV000301067	SCV000339272	benign	not specified	2016-02-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000553536	SCV000626507	benign	Glycogen storage disease, type II	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000553536	SCV001282566	uncertain significance	Glycogen storage disease, type II	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001558371	SCV001780304	likely benign	not provided	2019-02-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002379134	SCV002692946	likely benign	Cardiovascular phenotype	2022-02-16	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.