ClinVar Miner

Submissions for variant NM_001363.5(DKC1):c.5C>T (p.Ala2Val)

dbSNP: rs121912303
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001852640 SCV002301726 likely pathogenic Dyskeratosis congenita 2023-04-28 criteria provided, single submitter clinical testing This missense change has been observed in individuals with dyskeratosis congenita, bone marrow failure (PMID: 10364516, 11641517, 22664374, 33718801). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects DKC1 function (PMID: 26571381). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 38951). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2 of the DKC1 protein (p.Ala2Val).
3billion RCV000032202 SCV003841835 uncertain significance Dyskeratosis congenita, X-linked 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Missense changes are a common disease-causing mechanism. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.66). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with DKC1 related disorder (ClinVar ID: VCV000038951 / PMID: 10364516). However, the evidence of pathogenicity is insufficient at this time. Therefore, this variant is classified as VUS according to the recommendation of ACMG/AMP guideline.
GeneReviews RCV000032202 SCV000055794 not provided Dyskeratosis congenita, X-linked no assertion provided literature only
UniProtKB/Swiss-Prot RCV000032202 SCV000090833 not provided Dyskeratosis congenita, X-linked no assertion provided not provided

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