NM_000059.4(BRCA2):c.4165T>G (p.Phe1389Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 23, 2022
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:: RCV000759615.16

Allele description [Variation Report for NM_000059.4(BRCA2):c.4165T>G (p.Phe1389Val)]

NM_000059.4(BRCA2):c.4165T>G (p.Phe1389Val)

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.4165T>G (p.Phe1389Val)

HGVS:

NC_000013.11:g.32338520T>G
NG_012772.3:g.28041T>G
NM_000059.4:c.4165T>GMANE SELECT
NP_000050.2:p.Phe1389Val
NP_000050.3:p.Phe1389Val
LRG_293t1:c.4165T>G
LRG_293:g.28041T>G
LRG_293p1:p.Phe1389Val
NC_000013.10:g.32912657T>G
NM_000059.3:c.4165T>G

Protein change:

F1389V

Links:

dbSNP: rs1409088355

NCBI 1000 Genomes Browser:

rs1409088355

Molecular consequence:

NM_000059.4:c.4165T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000889045	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Dec 23, 2022)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28526081, 29470806, 26467025
SCV001473659	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Uncertain significance (May 8, 2020)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000889045

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Dec 23, 2022)

unknown

clinical testing

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

SCV001473659

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Uncertain significance
(May 8, 2020)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive detection of germline variants by MSK-IMPACT, a clinical diagnostic platform for solid tumor molecular oncology and concurrent cancer predisposition testing.

Cheng DT, Prasad M, Chekaluk Y, Benayed R, Sadowska J, Zehir A, Syed A, Wang YE, Somar J, Li Y, Yelskaya Z, Wong D, Robson ME, Offit K, Berger MF, Nafa K, Ladanyi M, Zhang L.

BMC Med Genomics. 2017 May 19;10(1):33. doi: 10.1186/s12920-017-0271-4.

PubMed [citation]

PMID:: 28526081
PMCID:: PMC5437632

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

Singh J, Thota N, Singh S, Padhi S, Mohan P, Deshwal S, Sur S, Ghosh M, Agarwal A, Sarin R, Ahmed R, Almel S, Chakraborti B, Raina V, DadiReddy PK, Smruti BK, Rajappa S, Dodagoudar C, Aggarwal S, Singhal M, Joshi A, Kumar R, et al.

Breast Cancer Res Treat. 2018 Jul;170(1):189-196. doi: 10.1007/s10549-018-4726-x. Epub 2018 Feb 22.

PubMed [citation]

PMID:: 29470806

See all PubMed Citations (3)

Details of each submission

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000889045.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The frequency of this variant in the general population, 0.0000042 (1/237332 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual affected with breast and/or ovarian cancer (PMID: 29470806 (2018)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.

#	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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001473659.1

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

Description

The BRCA2 c.4165T>G; p.Phe1389Val variant (rs1409088355) is reported in the literature in several individuals affected with breast and/or ovarian cancer (Singh 2018). This variant is found on a single chromosome in the Genome Aggregation Database (1/237332 alleles), indicating it is not a common polymorphism. The phenylalanine at codon 1389 is weakly conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. However, given the lack of clinical and functional data, the significance of the p.Phe1389Val variant is uncertain at this time. References: Singh J et al. Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations. Breast Cancer Res Treat. 2018 Jul;170(1):189-196.

#	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

Last Updated: Oct 26, 2024

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