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NM_032043.3(BRIP1):c.1105T>C (p.Tyr369His) AND multiple conditions

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 19, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000470192.12

Allele description [Variation Report for NM_032043.3(BRIP1):c.1105T>C (p.Tyr369His)]

NM_032043.3(BRIP1):c.1105T>C (p.Tyr369His)

Gene:
BRIP1:BRCA1 interacting DNA helicase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q23.2
Genomic location:
Preferred name:
NM_032043.3(BRIP1):c.1105T>C (p.Tyr369His)
HGVS:
  • NC_000017.11:g.61801288A>G
  • NG_007409.2:g.67272T>C
  • NM_032043.3:c.1105T>CMANE SELECT
  • NP_114432.2:p.Tyr369His
  • NP_114432.2:p.Tyr369His
  • LRG_300t1:c.1105T>C
  • LRG_300:g.67272T>C
  • LRG_300p1:p.Tyr369His
  • NC_000017.10:g.59878649A>G
  • NM_032043.2:c.1105T>C
  • p.Y369H
Protein change:
Y369H
Links:
dbSNP: rs587781325
NCBI 1000 Genomes Browser:
rs587781325
Molecular consequence:
  • NM_032043.3:c.1105T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
Breast cancer, familial; Hereditary breast cancer
Identifiers:
MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480
Name:
Fanconi anemia complementation group J
Identifiers:
MONDO: MONDO:0012187; MedGen: C1836860; Orphanet: 84; OMIM: 609054

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000547236Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jan 19, 2024)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002775262Fulgent Genetics, Fulgent Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Jan 14, 2022)
unknownclinical testing

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

Summary from all submissions

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

Citations

PubMed

No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, Luccarini C, Pooley KA, Shah M, Bolla MK, Wang Q, Dennis J, Ahmad J, Thompson ER, Damiola F, Pertesi M, Voegele C, Mebirouk N, Robinot N, Durand G, Forey N, Luben RN, et al.

J Med Genet. 2016 May;53(5):298-309. doi: 10.1136/jmedgenet-2015-103529. Epub 2016 Feb 26.

PubMed [citation]
PMID:
26921362
PMCID:
PMC4938802

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]
PMID:
28135145
PMCID:
PMC5455355
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000547236.10

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 369 of the BRIP1 protein (p.Tyr369His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer or colorectal cancer (PMID: 26921362, 28135145). ClinVar contains an entry for this variant (Variation ID: 140858). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BRIP1 protein function with a positive predictive value of 80%. 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

From Fulgent Genetics, Fulgent Genetics, SCV002775262.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024