Submissions for variant NM_000152.5(GAA):c.2571G>T (p.Leu857=)

gnomAD frequency: 0.00319  dbSNP: rs17853996

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000588826	SCV000522903	benign	not provided	2018-11-20	criteria provided, single submitter	clinical testing
Invitae	RCV001001793	SCV000626584	benign	Glycogen storage disease, type II	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000588826	SCV000695656	benign	not provided	2017-01-09	criteria provided, single submitter	clinical testing	Variant summary: The GAA c.2571G>T (p.Leu857Leu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 125/115766 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0119071 (122/10246). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic GAA variant (0.0042205), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001001793	SCV001159446	benign	Glycogen storage disease, type II	2019-11-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001001793	SCV001285667	likely benign	Glycogen storage disease, type II	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Ambry Genetics	RCV002450993	SCV002739546	likely benign	Cardiovascular phenotype	2022-02-20	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.