Submissions for variant NM_000152.5(GAA):c.1888+10_1888+11insC

gnomAD frequency: 0.00020  dbSNP: rs748036956

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000479968	SCV000572460	likely benign	not specified	2016-12-23	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000675233	SCV000709496	uncertain significance	not provided	2017-06-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000479968	SCV000917392	uncertain significance	not specified	2018-03-13	criteria provided, single submitter	clinical testing	Variant summary: GAA c.1888+10_1888+11insC alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant is found in gnomAD dataset exclusively in individuals of African descent at a frequency of 0.00076 (16/21150 chrs tested). This frequency is not higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00076 vs 0.0042), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1888+10_1888+11insC in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Another lab classified the variant as VUS. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae	RCV002063813	SCV002385906	likely benign	Glycogen storage disease, type II	2024-01-29	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003962346	SCV004783280	likely benign	GAA-related condition	2022-01-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Mayo Clinic Laboratories, Mayo Clinic	RCV000675233	SCV000800879	likely benign	not provided	2017-05-17	no assertion criteria provided	clinical testing