Submissions for variant NM_014908.4(DOLK):c.1dup (p.Met1fs)

gnomAD frequency: 0.00573  dbSNP: rs531969689

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000153163	SCV000269033	benign	not specified	2015-04-24	criteria provided, single submitter	clinical testing	c.1_2insA in exon 1 of DOLK: This variant is not expected to have clinical signi ficance because it does not alter the start codon and has been identified in 1.3 % (823/63350) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs531969689).
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000432254	SCV000511747	likely benign	not provided	2016-08-30	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
GeneDx	RCV000153163	SCV000564945	benign	not specified	2016-04-08	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.
Invitae	RCV001080976	SCV000638513	benign	DK1-congenital disorder of glycosylation	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002415646	SCV002721553	likely benign	Cardiovascular phenotype	2018-12-27	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, LabCorp	RCV000153163	SCV004029113	benign	not specified	2023-07-31	criteria provided, single submitter	clinical testing	Variant summary: The DOLK c.1dupA variant allele was found at a frequency of 0.0065 in 247242 control chromosomes, predominantly at a frequency of 0.011 within the Non-Finnish European subpopulation in the gnomAD database, including 9 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.6 fold of the estimated maximal expected allele frequency for a pathogenic variant in DOLK causing Cardiomyopathy phenotype (0.0071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.1dupA in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000432254	SCV004156449	benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	DOLK: BS1, BS2
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001080976	SCV004564030	benign	DK1-congenital disorder of glycosylation	2023-10-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000153163	SCV000202630	benign	not specified	2014-02-28	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000432254	SCV001978024	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000153163	SCV001979640	benign	not specified		no assertion criteria provided	clinical testing