NM_000059.4(BRCA2):c.476T>C (p.Val159Ala) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 22, 2022
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:: RCV001306302.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.476T>C (p.Val159Ala)]

NM_000059.4(BRCA2):c.476T>C (p.Val159Ala)

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.476T>C (p.Val159Ala)

HGVS:

NC_000013.11:g.32326242T>C
NG_012772.3:g.15763T>C
NM_000059.4:c.476T>CMANE SELECT
NP_000050.2:p.Val159Ala
NP_000050.3:p.Val159Ala
LRG_293t1:c.476T>C
LRG_293:g.15763T>C
LRG_293p1:p.Val159Ala
NC_000013.10:g.32900379T>C
NM_000059.3:c.476T>C

Protein change:

V159A

Links:

dbSNP: rs81002884

NCBI 1000 Genomes Browser:

rs81002884

Molecular consequence:

NM_000059.4:c.476T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Potamopyrgus estuarinus mitochondrion, complete genome
Potamopyrgus estuarinus mitochondrion, complete genome
gi|2575786108|gb|OR426589.1|

Nucleotide
cytochrome b, partial (mitochondrion) [Megascops atricapilla]
cytochrome b, partial (mitochondrion) [Megascops atricapilla]
gi|22796951|emb|CAC79751.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001495669	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 22, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30254663, 34034685, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001495669

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 22, 2022)

germline

clinical testing

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

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

Citations

PubMed

Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?

Zuntini R, Ferrari S, Bonora E, Buscherini F, Bertonazzi B, Grippa M, Godino L, Miccoli S, Turchetti D.

Front Genet. 2018;9:378. doi: 10.3389/fgene.2018.00378.

PubMed [citation]

PMID:: 30254663
PMCID:: PMC6141711

Comprehensive analysis of DNA damage repair genes reveals pathogenic variants beyond BRCA and suggests the need for extensive genetic testing in pancreatic cancer.

Rapposelli IG, Zampiga V, Cangini I, Arcangeli V, Ravegnani M, Valgiusti M, Pini S, Tamberi S, Bartolini G, Passardi A, Martinelli G, Calistri D, Frassineti GL, Falcini F, Danesi R.

BMC Cancer. 2021 May 26;21(1):611. doi: 10.1186/s12885-021-08368-5.

PubMed [citation]

PMID:: 34034685
PMCID:: PMC8152298

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001495669.4

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

Description

Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 495466). This missense change has been observed in individual(s) with kidney cancer (PMID: 30254663, 34034685). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 159 of the BRCA2 protein (p.Val159Ala). 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

Last Updated: Sep 29, 2024

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