ClinVar Miner

Submissions for variant NM_014908.4(DOLK):c.1201_1202del (p.Ser401fs)

gnomAD frequency: 0.00002  dbSNP: rs919111760
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001373869 SCV001570601 uncertain significance DK1-congenital disorder of glycosylation 2021-08-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser401Trpfs*30) in the DOLK gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 138 amino acid(s) of the DOLK protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with DOLK-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the DOLK protein in which other variant(s) (p.Gln483Lys) have been observed in individuals with DOLK-related conditions (PMID: 24144945). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002350719 SCV002652250 likely pathogenic Cardiovascular phenotype 2022-01-05 criteria provided, single submitter clinical testing The c.1201_1202delAG variant, located in coding exon 1 of the DOLK gene, results from a deletion of two nucleotides at nucleotide positions 1201 to 1202, causing a translational frameshift with a predicted alternate stop codon (p.S401Wfs*30). This alteration is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 25% of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001373869 SCV002784442 uncertain significance DK1-congenital disorder of glycosylation 2021-07-26 criteria provided, single submitter clinical testing

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