Submissions for variant NM_002878.4(RAD51D):c.873C>T (p.Arg291=)

gnomAD frequency: 0.00399  dbSNP: rs140848654

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212973	SCV000171278	benign	not specified	2014-01-09	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000127699	SCV000213971	likely benign	Hereditary cancer-predisposing syndrome	2014-07-22	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	RCV000204704	SCV000262502	benign	Breast-ovarian cancer, familial, susceptibility to, 4	2025-02-03	criteria provided, single submitter	clinical testing
Counsyl	RCV000204704	SCV000488521	benign	Breast-ovarian cancer, familial, susceptibility to, 4	2016-05-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000127699	SCV000686494	benign	Hereditary cancer-predisposing syndrome	2015-04-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000212973	SCV000806590	benign	not specified	2017-08-11	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000204704	SCV000884440	benign	Breast-ovarian cancer, familial, susceptibility to, 4	2021-05-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477533	SCV000888613	benign	not provided	2022-07-18	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149872	SCV003838191	benign	Breast and/or ovarian cancer	2022-05-02	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000204704	SCV004017711	benign	Breast-ovarian cancer, familial, susceptibility to, 4	2023-04-06	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000212973	SCV005872519	benign	not specified	2025-03-04	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356097	SCV001551166	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The RAD51D p.Arg291= variant was not identified in the literature nor was it identified in the Cosmic and Zhejiang Colon Cancer Database. The variant was also identified in dbSNP (ID: rs140848654) “With Likely benign allele”, ClinVar (classified benign by GeneDx, Invitae, Counsyl; and likely benign by Ambry Genetics, Illumina), Clinvitae (4X) and in control databases in 325 (2 homozygous) of 277174 chromosomes at a frequency of 0.001 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 301 (2 homozygous) of 24032 chromosomes (frequency: 0.01), Other in 3 of 6460 chromosomes (frequency: 0005), Latino in 17 of 34418 chromosomes (frequency: 0.0005), European Non-Finnish in 4 of 126672 chromosomes (frequency: 00003). The p.Arg291= 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 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.