Submissions for variant NM_014908.4(DOLK):c.700A>G (p.Met234Val)

gnomAD frequency: 0.00102  dbSNP: rs139787271

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723494	SCV000113612	uncertain significance	not provided	2012-10-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000723494	SCV000574277	likely benign	not provided	2021-04-20	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 23757202, 23806237)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084826	SCV000638521	likely benign	DK1-congenital disorder of glycosylation	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001084826	SCV001331467	uncertain significance	DK1-congenital disorder of glycosylation	2017-04-28	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Ambry Genetics	RCV002371930	SCV002668144	likely benign	Cardiovascular phenotype	2023-11-21	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.
Revvity Omics, Revvity	RCV001084826	SCV003832232	uncertain significance	DK1-congenital disorder of glycosylation	2020-03-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004782051	SCV005395229	likely benign	not specified	2024-09-23	criteria provided, single submitter	clinical testing	Variant summary: DOLK c.700A>G (p.Met234Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0012 in 251482 control chromosomes, predominantly at a frequency of 0.002 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in DOLK causing DK1-Congenital Disorder Of Glycosylation phenotype (0.0011). To our knowledge, no occurrence of c.700A>G in individuals affected with DK1-Congenital Disorder Of Glycosylation and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 95647). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003915087	SCV004729549	likely benign	DOLK-related disorder	2022-06-01	no assertion criteria provided	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).