Submissions for variant NM_032043.3(BRIP1):c.2406C>T (p.Asp802=)

gnomAD frequency: 0.00002  dbSNP: rs748981650

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000582200	SCV000689334	likely benign	Hereditary cancer-predisposing syndrome	2015-04-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001083394	SCV001016874	likely benign	Familial cancer of breast; Fanconi anemia complementation group J	2024-02-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000874669	SCV001134014	likely benign	not provided	2019-07-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000582200	SCV001176259	likely benign	Hereditary cancer-predisposing syndrome	2017-01-12	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.
GeneDx	RCV000874669	SCV001945441	likely benign	not provided	2019-05-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV004787982	SCV005405573	benign	Familial cancer of breast	2024-09-04	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	RCV000874669	SCV001551650	uncertain significance	not provided		no assertion criteria provided	clinical testing	The BRIP1 p.Asp802= variant was not identified in the literature nor was it identified in the ClinVar, Cosmic, MutDB, and Zhejiang Colon Cancer Database. The variant was identified in dbSNP (ID: rs748981650), and in control databases in 10 of 275524 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: “Other” in 1 of 6428 chromosomes (freq: 0.0002), and East Asian in 9 of 18502 chromosomes (freq: 0.0005); but not in the African, Latino, European Non-Finnish, Ashkenazi Jewish, European Finnish, and South Asian populations. The p.Asp802= 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. This variant is classified as a variant of uncertain significance.