Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001591127 | SCV000569348 | benign | not provided | 2018-05-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001271973 | SCV001471592 | benign | Glycogen storage disease, type II | 2022-03-07 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001824798 | SCV002074255 | benign | not specified | 2022-01-14 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.858+17_858+23delCGGGCGG alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0015 in 274012 control chromosomes, predominantly at a frequency of 0.016 within the African or African-American subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 4 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.858+17_858+23delCGGGCGG in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cited the variant as benign (n=2) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as benign. |
Natera, |
RCV001271973 | SCV001453598 | likely benign | Glycogen storage disease, type II | 2020-09-16 | no assertion criteria provided | clinical testing | |
Gene |
RCV001591127 | SCV001826669 | likely benign | not provided | 2018-09-04 | flagged submission | clinical testing |