Submissions for variant NM_002878.4(RAD51D):c.257T>G (p.Ile86Ser)

dbSNP: rs1312421615

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002021110	SCV002298306	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2023-08-23	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51D protein function. ClinVar contains an entry for this variant (Variation ID: 1515461). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 86 of the RAD51D protein (p.Ile86Ser).
Ambry Genetics	RCV002425424	SCV002740365	uncertain significance	Hereditary cancer-predisposing syndrome	2023-04-24	criteria provided, single submitter	clinical testing	The p.I86S variant (also known as c.257T>G), located in coding exon 3 of the RAD51D gene, results from a T to G substitution at nucleotide position 257. The isoleucine at codon 86 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV002425424	SCV004357175	uncertain significance	Hereditary cancer-predisposing syndrome	2022-10-10	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with serine at codon 86 of the RAD51D protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.