Submissions for variant NM_032043.3(BRIP1):c.1566A>G (p.Ser522=)

dbSNP: rs985465808

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000439557	SCV000512418	likely benign	not specified	2017-04-10	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081610	SCV000633560	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2025-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000566761	SCV000666189	likely benign	Hereditary cancer-predisposing syndrome	2015-08-05	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.
Color Diagnostics, LLC DBA Color Health	RCV000566761	SCV000689275	likely benign	Hereditary cancer-predisposing syndrome	2017-06-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000543495	SCV001134006	likely benign	not provided	2018-10-26	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004786687	SCV005404366	benign	Familial cancer of breast	2024-08-28	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.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001357727	SCV001553280	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The BRIP1 p.Ser522= variant was not identified in the literature nor was it identified in the Cosmic, Zhejiang University Database. The variant was identified in dbSNP (ID: rs985465808) as With Likely benign allele, and in ClinVar (classified as likely benign by GeneDx, Invitae, Ambry Genetics, Color Genomics). The variant was identified in control databases in 1 of 246166 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). It was observed in the African population in 1 of 15300 chromosomes (freq: 0.0001), but not in the “Other”, Latino, European, Ashkenazi Jewish, East Asian, Finnish, and South Asian populations. The p.Ser522 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, HumanSpliceFinder) 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.