NM_000059.4(BRCA2):c.323A>G (p.Asn108Ser) AND Hereditary breast ovarian cancer syndrome

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 1, 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:: RCV001372390.6

Allele description

NM_000059.4(BRCA2):c.323A>G (p.Asn108Ser)

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.323A>G (p.Asn108Ser)

HGVS:

NC_000013.11:g.32325082A>G
NG_012772.3:g.14603A>G
NM_000059.4:c.323A>GMANE SELECT
NP_000050.2:p.Asn108Ser
NP_000050.3:p.Asn108Ser
LRG_293t1:c.323A>G
LRG_293:g.14603A>G
LRG_293p1:p.Asn108Ser
NC_000013.10:g.32899219A>G
NM_000059.3:c.323A>G
U43746.1:n.551A>G
p.N108S

Nucleotide change:

551A>G

Protein change:

N108S

Links:

dbSNP: rs80358568

NCBI 1000 Genomes Browser:

rs80358568

Molecular consequence:

NM_000059.4:c.323A>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
SCV001569039	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 1, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30606148, 35918668, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001569039

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 1, 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

Prevalence of BRCA1 and BRCA2 pathogenic and likely pathogenic variants in non-selected ovarian carcinoma patients in Brazil.

Cotrim DP, Ribeiro ARG, Paixão D, de Queiroz Soares DC, Jbili R, Pandolfi NC, Cezana C, de Cássia Mauro C, Mantoan H, Bovolim G, de Brot L, Torrezan GT, Carraro DM, Baiocchi G, da Cruz Formiga MN, da Costa AABA.

BMC Cancer. 2019 Jan 3;19(1):4. doi: 10.1186/s12885-018-5235-3.

PubMed [citation]

PMID:: 30606148
PMCID:: PMC6319008

Germline variants profiling of BRCA1 and BRCA2 in Chinese Hakka breast and ovarian cancer patients.

Zhang Y, Wu H, Yu Z, Li L, Zhang J, Liang X, Huang Q.

BMC Cancer. 2022 Aug 2;22(1):842. doi: 10.1186/s12885-022-09943-0.

PubMed [citation]

PMID:: 35918668
PMCID:: PMC9347172

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001569039.4

#	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 asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 108 of the BRCA2 protein (p.Asn108Ser). This variant is present in population databases (rs80358568, gnomAD 0.04%). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 30606148, 35918668). ClinVar contains an entry for this variant (Variation ID: 51430). 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 8, 2024

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