NM_000059.4(BRCA2):c.2471T>C (p.Leu824Ser) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 31, 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:: RCV000476153.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.2471T>C (p.Leu824Ser)]

NM_000059.4(BRCA2):c.2471T>C (p.Leu824Ser)

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.2471T>C (p.Leu824Ser)

HGVS:

NC_000013.11:g.32336826T>C
NG_012772.3:g.26347T>C
NM_000059.4:c.2471T>CMANE SELECT
NP_000050.2:p.Leu824Ser
NP_000050.3:p.Leu824Ser
LRG_293t1:c.2471T>C
LRG_293:g.26347T>C
LRG_293p1:p.Leu824Ser
NC_000013.10:g.32910963T>C
NM_000059.3:c.2471T>C
p.L824S

Protein change:

L824S

Links:

dbSNP: rs397507631

NCBI 1000 Genomes Browser:

rs397507631

Molecular consequence:

NM_000059.4:c.2471T>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
SCV000549601	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 31, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 28664449, 31837001, 32068069, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000549601

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 31, 2023)

germline

clinical testing

PubMed (4)
[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

Analysis of BRCA1/2 mutation spectrum and prevalence in unselected Chinese breast cancer patients by next-generation sequencing.

Li G, Guo X, Tang L, Chen M, Luo X, Peng L, Xu X, Wang S, Xiao Z, Yi W, Dai L, Wang J.

J Cancer Res Clin Oncol. 2017 Oct;143(10):2011-2024. doi: 10.1007/s00432-017-2465-8. Epub 2017 Jun 29.

PubMed [citation]

PMID:: 28664449

Discovery of rare coding variants in OGDHL and BRCA2 in relation to breast cancer risk in Chinese women.

Guo X, Long J, Chen Z, Shu XO, Xiang YB, Wen W, Zeng C, Gao YT, Cai Q, Zheng W.

Int J Cancer. 2020 Apr 15;146(8):2175-2181. doi: 10.1002/ijc.32825. Epub 2019 Dec 27.

PubMed [citation]

PMID:: 31837001
PMCID:: PMC7453427

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000549601.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

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: 133734). This missense change has been observed in individual(s) with breast and/ovarian cancer (PMID: 28664449, 31837001, 32068069). This variant is present in population databases (rs397507631, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 824 of the BRCA2 protein (p.Leu824Ser).

#	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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