NM_000059.4(BRCA2):c.3540G>C (p.Lys1180Asn) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 27, 2023
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:: RCV000206612.12

Allele description [Variation Report for NM_000059.4(BRCA2):c.3540G>C (p.Lys1180Asn)]

NM_000059.4(BRCA2):c.3540G>C (p.Lys1180Asn)

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.3540G>C (p.Lys1180Asn)

HGVS:

NC_000013.11:g.32337895G>C
NG_012772.3:g.27416G>C
NM_000059.4:c.3540G>CMANE SELECT
NP_000050.2:p.Lys1180Asn
NP_000050.3:p.Lys1180Asn
LRG_293t1:c.3540G>C
LRG_293:g.27416G>C
LRG_293p1:p.Lys1180Asn
NC_000013.10:g.32912032G>C
NM_000059.3:c.3540G>C

Protein change:

K1180N

Links:

dbSNP: rs864622363

NCBI 1000 Genomes Browser:

rs864622363

Molecular consequence:

NM_000059.4:c.3540G>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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000260309	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30093976, 32101877, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000260309

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 2023)

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

Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.

Chan GHJ, Ong PY, Low JJH, Kong HL, Ow SGW, Tan DSP, Lim YW, Lim SE, Lee SC.

Oncotarget. 2018 Jul 17;9(55):30649-30660. doi: 10.18632/oncotarget.25769.

PubMed [citation]

PMID:: 30093976
PMCID:: PMC6078133

Frequency of BRCA1 and BRCA2 Mutations in Individuals with Breast and Ovarian Cancer in a Chinese Hakka Population Using Next-Generation Sequencing.

Wu H, Wang Q, Guo X, Liu Q, Zhang Q, Huang Q, Yu Z.

Hum Hered. 2019;84(4-5):160-169. doi: 10.1159/000505268. Epub 2020 Feb 26.

PubMed [citation]

PMID:: 32101877

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000260309.9

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

Description

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. 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. ClinVar contains an entry for this variant (Variation ID: 220061). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 30093976, 32101877). This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1180 of the BRCA2 protein (p.Lys1180Asn).

#	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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