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NM_000059.4(BRCA2):c.663T>G (p.Phe221Leu) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Sep 11, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000781125.11

Allele description [Variation Report for NM_000059.4(BRCA2):c.663T>G (p.Phe221Leu)]

NM_000059.4(BRCA2):c.663T>G (p.Phe221Leu)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.4(BRCA2):c.663T>G (p.Phe221Leu)
Other names:
NM_000059.4(BRCA2):c.663T>G; p.Phe221Leu
HGVS:
  • NC_000013.11:g.32329474T>G
  • NG_012772.3:g.18995T>G
  • NM_000059.4:c.663T>GMANE SELECT
  • NP_000050.2:p.Phe221Leu
  • NP_000050.3:p.Phe221Leu
  • LRG_293t1:c.663T>G
  • LRG_293:g.18995T>G
  • LRG_293p1:p.Phe221Leu
  • NC_000013.10:g.32903611T>G
  • NM_000059.3:c.663T>G
  • U43746.1:n.891T>G
  • p.F221L
Nucleotide change:
891T>G
Protein change:
F221L
Links:
dbSNP: rs80358891
NCBI 1000 Genomes Browser:
rs80358891
Molecular consequence:
  • NM_000059.4:c.663T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000918973Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Sep 11, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Mutation screening of RAD51C in high-risk breast and ovarian cancer families.

Lu W, Wang X, Lin H, Lindor NM, Couch FJ.

Fam Cancer. 2012 Sep;11(3):381-5. doi: 10.1007/s10689-012-9523-9.

PubMed [citation]
PMID:
22476429
PMCID:
PMC3418444

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000918973.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: BRCA2 c.663T>G (p.Phe221Leu) results in a non-conservative amino acid change in the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 245048 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.663T>G has been reported in the literature in an individual affected with breast cancer from a high-risk breast/ovarian cancer family (Lu_2012). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 22476429). Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2024