NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu) AND Hereditary breast and ovarian cancer syndrome

Clinical significance:Uncertain significance (Last evaluated: Oct 20, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001344736.1

Allele description [Variation Report for NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)]

NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)

Gene:
BRCA1:BRCA1 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.31
Genomic location:
Preferred name:
NM_007294.4(BRCA1):c.1383T>A (p.Phe461Leu)
HGVS:
  • NC_000017.11:g.43094148A>T
  • NG_005905.2:g.123836T>A
  • NM_007294.3:c.1383T>A
  • NM_007294.4:c.1383T>AMANE SELECT
  • NM_007297.4:c.1242T>A
  • NM_007298.3:c.787+596T>A
  • NM_007299.4:c.787+596T>A
  • NM_007300.4:c.1383T>A
  • NP_009225.1:p.Phe461Leu
  • NP_009225.1:p.Phe461Leu
  • NP_009228.2:p.Phe414Leu
  • NP_009231.2:p.Phe461Leu
  • LRG_292t1:c.1383T>A
  • LRG_292:g.123836T>A
  • LRG_292p1:p.Phe461Leu
  • NC_000017.10:g.41246165A>T
  • NM_007294.4:c.1383T>A
  • NR_027676.2:n.1560T>A
  • P38398:p.Phe461Leu
  • U14680.1:n.1502T>A
  • p.F461L
Protein change:
F414L
Links:
UniProtKB: P38398#VAR_007765; dbSNP: rs56046357
NCBI 1000 Genomes Browser:
rs56046357
Molecular consequence:
  • NM_007298.3:c.787+596T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007299.4:c.787+596T>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_007294.3:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007294.4:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007297.4:c.1242T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_007300.4:c.1383T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_027676.2:n.1560T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC)
Identifiers:
MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001538812Invitaecriteria provided, single submitter
Uncertain significance
(Oct 20, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

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

Sequence variant discovery in DNA repair genes from radiosensitive and radiotolerant prostate brachytherapy patients.

Pugh TJ, Keyes M, Barclay L, Delaney A, Krzywinski M, Thomas D, Novik K, Yang C, Agranovich A, McKenzie M, Morris WJ, Olive PL, Marra MA, Moore RA.

Clin Cancer Res. 2009 Aug 1;15(15):5008-16. doi: 10.1158/1078-0432.CCR-08-3357. Epub 2009 Jul 28.

PubMed [citation]
PMID:
19638463
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001538812.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces phenylalanine with leucine at codon 461 of the BRCA1 protein (p.Phe461Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with breast, ovarian, prostate and gastric cancer (PMID: 22476429, 19638463, 9609997). ClinVar contains an entry for this variant (Variation ID: 54228). Based on a multifactorial likelihood algorithm using genetic and statistical data, this variant has been determined to have a low probability of being pathogenic (PMID: 31131967). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 18, 2021

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