Submissions for variant NM_002878.4(RAD51D):c.329G>C (p.Gly110Ala)

dbSNP: rs587780103

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000217137	SCV000273164	uncertain significance	Hereditary cancer-predisposing syndrome	2024-07-01	criteria provided, single submitter	clinical testing	The p.G110A variant (also known as c.329G>C), located in coding exon 4 of the RAD51D gene, results from a G to C substitution at nucleotide position 329. The glycine at codon 110 is replaced by alanine, 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. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health	RCV000217137	SCV000908962	uncertain significance	Hereditary cancer-predisposing syndrome	2021-08-24	criteria provided, single submitter	clinical testing	This missense variant replaces glycine with alanine at codon 110 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 been reported in an individual affected with breast and/or ovarian (PMID: 29470806). This variant has been identified in 1/251280 chromosomes 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001038664	SCV001202143	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-04-22	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 110 of the RAD51D protein (p.Gly110Ala). This variant is present in population databases (rs587780103, gnomAD 0.003%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 229820). 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 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.
Baylor Genetics	RCV001038664	SCV004200405	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2023-06-20	criteria provided, single submitter	clinical testing
GeneDx	RCV004721305	SCV005327243	uncertain significance	not provided	2024-01-04	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast and/or ovarian cancer (PMID: 29470806); This variant is associated with the following publications: (PMID: 14704354, 21111057, 29470806)