ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.241T>A (p.Phe81Ile) (rs80358507)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000217504 SCV000272958 likely benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031366 SCV000146428 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000217504 SCV000683483 uncertain significance Hereditary cancer-predisposing syndrome 2018-05-30 criteria provided, single submitter clinical testing
Counsyl RCV000031366 SCV000784869 uncertain significance Breast-ovarian cancer, familial 2 2017-01-18 criteria provided, single submitter clinical testing
GeneDx RCV000586268 SCV000210434 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.241T>A at the cDNA level, p.Phe81Ile (F81I) at the protein level, and results in the change of a Phenylalanine to an Isoleucine (TTC>ATC). Using alternate nomenclature, this variant would be defined as BRCA2 469T>A. This variant was observed in at least one individual with prostate cancer (Kote-Jarai 2011). BRCA2 Phe81Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Phenylalanine and Isoleucine share similar properties, this is considered a conservative amino acid substitution. BRCA2 Phe81Ile occurs at a position that is conserved across species and is not located in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Phe81Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000586268 SCV000694607 uncertain significance not provided 2016-08-08 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.241T>A (p.Phe81Ile) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant is located in the RING domain (InterPro). This variant was found in 2/121152 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.00003 (2/66608). This frequency is lower than the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant is reported in at least one individual with prostate cancer in literature (Kote-Jarai_2001). It has also been reported in several subjects undergoing BRCA1/2 testing by clinical laboratories/databases. Clinical diagnostic laboratories/reputable databases have provided conflicting classifications ranging from uncertain singnificance to benign, without evidences to independently evaluate. There are no published functional studies for the variant. Taken together, this variant is currently classified as a Variant of Uncertain Significance.
Invitae RCV000043988 SCV000072001 likely benign Hereditary breast and ovarian cancer syndrome 2017-11-08 criteria provided, single submitter clinical testing
Mendelics RCV000043988 SCV000838725 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031366 SCV000053971 benign Breast-ovarian cancer, familial 2 2010-06-04 no assertion criteria provided clinical testing

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