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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000547236	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 19, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26921362, 28135145, 28492532
SCV002775262	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 14, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000547236

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 19, 2024)

germline

clinical testing

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

SCV002775262

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 14, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002775262.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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