Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521128 | SCV000618278 | likely benign | not specified | 2018-01-23 | 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. |
| Labcorp Genetics |
RCV000527496 | SCV000638510 | benign | DK1-congenital disorder of glycosylation | 2025-02-02 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000527496 | SCV001329957 | uncertain significance | DK1-congenital disorder of glycosylation | 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. |
| Ambry Genetics | RCV002395250 | SCV002700409 | likely benign | Cardiovascular phenotype | 2019-05-30 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000521128 | SCV004122474 | likely benign | not specified | 2023-10-31 | criteria provided, single submitter | clinical testing | Variant summary: DOLK c.1481A>G (p.Asp494Gly) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 152156 control chromosomes, predominantly at a frequency of 0.013 within the Ashkenazi Jewish subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 12 fold of the estimated maximal expected allele frequency for a pathogenic variant in DOLK causing DK1-Congenital Disorder Of Glycosylation phenotype (0.0011), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Ashkenazi Jewish origin. c.1481A>G has been reported in the literature in one individual affected with DK1-Congenital Disorder Of Glycosylation (Jones_2013). The report does not provide unequivocal conclusions about association of the variant with DK1-Congenital Disorder Of Glycosylation. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 23806237). Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified this variant as uncertain significance (n=1), likely benign (n=2) and benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |