Submissions for variant NM_058216.3(RAD51C):c.463G>A (p.Ala155Thr)

dbSNP: rs755879664

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000690938	SCV000818669	uncertain significance	Fanconi anemia complementation group O	2023-11-08	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 155 of the RAD51C protein (p.Ala155Thr). This variant is present in population databases (rs755879664, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 570140). 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 RAD51C protein function with a negative predictive value of 80%. 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.
Color Diagnostics, LLC DBA Color Health	RCV000775204	SCV000909444	uncertain significance	Hereditary cancer-predisposing syndrome	2018-12-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001575212	SCV001802161	uncertain significance	not provided	2020-02-20	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28481359)
Ambry Genetics	RCV000775204	SCV002639885	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-09	criteria provided, single submitter	clinical testing	The p.A155T variant (also known as c.463G>A), located in coding exon 3 of the RAD51C gene, results from a G to A substitution at nucleotide position 463. The alanine at codon 155 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002493171	SCV002775492	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2021-08-31	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV003321717	SCV004026858	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003403601	SCV004111383	uncertain significance	RAD51C-related condition	2022-12-27	criteria provided, single submitter	clinical testing	The RAD51C c.463G>A variant is predicted to result in the amino acid substitution p.Ala155Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56774112-G-A) and is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/570140/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.