NM_000059.4(BRCA2):c.240A>G (p.Ile80Met) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2024
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:: RCV000043985.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.240A>G (p.Ile80Met)]

NM_000059.4(BRCA2):c.240A>G (p.Ile80Met)

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.240A>G (p.Ile80Met)

HGVS:

NC_000013.11:g.32319249A>G
NG_012772.3:g.8770A>G
NG_017006.2:g.1115T>C
NM_000059.4:c.240A>GMANE SELECT
NP_000050.2:p.Ile80Met
NP_000050.3:p.Ile80Met
LRG_293t1:c.240A>G
LRG_293:g.8770A>G
LRG_293p1:p.Ile80Met
NC_000013.10:g.32893386A>G
NM_000059.3:c.240A>G
U43746.1:n.468A>G
p.I80M

Protein change:

I80M

Links:

dbSNP: rs80358505

NCBI 1000 Genomes Browser:

rs80358505

Molecular consequence:

NM_000059.4:c.240A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000071998	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10923033, 28678401, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000071998

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2024)

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

The breast cancer information core: database design, structure, and scope.

Szabo C, Masiello A, Ryan JF, Brody LC.

Hum Mutat. 2000;16(2):123-31.

PubMed [citation]

PMID:: 10923033

Assessing the spectrum of germline variation in Fanconi anemia genes among patients with head and neck carcinoma before age 50.

Chandrasekharappa SC, Chinn SB, Donovan FX, Chowdhury NI, Kamat A, Adeyemo AA, Thomas JW, Vemulapalli M, Hussey CS, Reid HH, Mullikin JC, Wei Q, Sturgis EM.

Cancer. 2017 Oct 15;123(20):3943-3954. doi: 10.1002/cncr.30802. Epub 2017 Jul 5.

PubMed [citation]

PMID:: 28678401
PMCID:: PMC5853120

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000071998.10

#	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 isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 80 of the BRCA2 protein (p.Ile80Met). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or head and neck squamous cell carcinoma (PMID: 10923033, 28678401). ClinVar contains an entry for this variant (Variation ID: 51277). 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 not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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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