Submissions for variant NM_002878.4(RAD51D):c.2del (p.Met1fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003216440	SCV003911837	likely pathogenic	Hereditary cancer-predisposing syndrome	2024-03-18	criteria provided, single submitter	clinical testing	The p.M1? variant (also known as c.2delT) is located in coding exon 1 of the RAD51D gene and results from a deletion of one thymine at nucleotide position 2. This alters the methionine residue at the initiation codon (ATG). A second in-frame methionine exists in RAD51D at amino acid position 16; however, this is predicted to be a relatively weak translation initiation site, and based on internal structural analysis, the first 15 amino acids are predicted to play an important role in protein function (Kim YM et al. Int J Biochem Cell Biol, 2011 Mar;43:416-22). 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. In addition to the clinical data presented in the literature, 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.