ClinVar Miner

Submissions for variant NM_002878.4(RAD51D):c.2T>C (p.Met1Thr)

dbSNP: rs1064794619
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521853 SCV000619303 likely pathogenic not provided 2022-09-24 criteria provided, single submitter clinical testing Initiation codon variant in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 24130102, 26681312)
Labcorp Genetics (formerly Invitae), Labcorp RCV000809878 SCV000950059 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 4 2018-07-20 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the RAD51D mRNA. The next in-frame methionine is located at codon 16. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD51D-related disease. ClinVar contains an entry for this variant (Variation ID: 450694). 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. Experimental studies have not been reported for this initiation codon variant and it is currently unknown if translation is rescued by a downstream methionine.
Ambry Genetics RCV004023579 SCV005020114 likely pathogenic Hereditary cancer-predisposing syndrome 2023-11-22 criteria provided, single submitter clinical testing The p.M1? variant (also known as c.2T>C) is located in coding exon 1 of the RAD51D gene and results from a T to C substitution at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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