Submissions for variant NM_002878.4(RAD51D):c.27C>T (p.Cys9=)

gnomAD frequency: 0.00001  dbSNP: rs200487648

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165490	SCV000216221	likely benign	Hereditary cancer-predisposing syndrome	2014-09-12	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000229283	SCV000287704	likely benign	Breast-ovarian cancer, familial, susceptibility to, 4	2025-01-06	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165490	SCV000686439	likely benign	Hereditary cancer-predisposing syndrome	2015-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001284345	SCV000714349	likely benign	not provided	2019-01-04	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284345	SCV001470087	likely benign	not provided	2020-03-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165490	SCV002534792	likely benign	Hereditary cancer-predisposing syndrome	2021-11-22	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001358354	SCV001554060	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The RAD51D p.Cys9= variant was not identified in the literature. The variant was identified in dbSNP (ID: rs200487648) as “With Likely benign allele” and ClinVar (classified likely benign by Ambry Genetics, Invitae, Color and GeneDx). The variant was identified in control databases in 10 of 242490 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017), observed in the following populations: Other in 1 of 5456 chromosomes (freq: 0.0002) and East Asian in 9 of 17198 chromosomes (freq: 0.0005), while not observed in the African, Latino, European, Ashkenazi Jewish, Finnish, or South Asian populations. The p.Cys9= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.