Submissions for variant NM_002878.4(RAD51D):c.28C>T (p.Pro10Ser)

dbSNP: rs1555570500

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000568308	SCV000663836	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-10	criteria provided, single submitter	clinical testing	The p.P10S variant (also known as c.28C>T), located in coding exon 1 of the RAD51D gene, results from a C to T substitution at nucleotide position 28. The proline at codon 10 is replaced by serine, an amino acid with similar properties. This amino acid position is highly 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	RCV000568308	SCV000686440	uncertain significance	Hereditary cancer-predisposing syndrome	2023-01-24	criteria provided, single submitter	clinical testing	This missense variant replaces proline with serine at codon 10 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 RAD51D-related disorders 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589109	SCV000698095	uncertain significance	not provided	2016-09-09	criteria provided, single submitter	clinical testing	Variant summary: The RAD51D c.28C>T (p.Pro10Ser) variant involves the alteration of a conserved nucleotide. Pro10 is conserved in mammals, but is not located in a known functional domain. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was absent in 119672 control chromosomes and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000798462	SCV000938080	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-09-14	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 10 of the RAD51D protein (p.Pro10Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 480536). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx	RCV000589109	SCV005421191	uncertain significance	not provided	2024-06-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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: 21111057)