NM_000059.4(BRCA2):c.5590G>A (p.Asp1864Asn) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 28, 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:: RCV000456720.7

Allele description [Variation Report for NM_000059.4(BRCA2):c.5590G>A (p.Asp1864Asn)]

NM_000059.4(BRCA2):c.5590G>A (p.Asp1864Asn)

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.5590G>A (p.Asp1864Asn)

HGVS:

NC_000013.11:g.32339945G>A
NG_012772.3:g.29466G>A
NM_000059.4:c.5590G>AMANE SELECT
NP_000050.2:p.Asp1864Asn
NP_000050.3:p.Asp1864Asn
LRG_293t1:c.5590G>A
LRG_293:g.29466G>A
LRG_293p1:p.Asp1864Asn
NC_000013.10:g.32914082G>A
NM_000059.3:c.5590G>A
p.D1864N

Protein change:

D1864N

Links:

dbSNP: rs587781536

NCBI 1000 Genomes Browser:

rs587781536

Molecular consequence:

NM_000059.4:c.5590G>A - 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
SCV000549768	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 28, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 22126563, 26852015, 27257965, 30415210, 30725392, 31161121, 31907386, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000549768

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 28, 2024)

germline

clinical testing

PubMed (8)
[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

Frequent germline mutation in the BRCA2 gene in esophageal squamous cell carcinoma patients from a low-risk Chinese population.

Zhong L, Zhu ZZ, Shen Y, Sun G, Zhao X, Zhang S, Yin X, Zhu J, Xu Z, Zhu G.

Asian Pac J Cancer Prev. 2011;12(7):1771-6.

PubMed [citation]

PMID:: 22126563

Novel germline mutations and unclassified variants of BRCA1 and BRCA2 genes in Chinese women with familial breast/ovarian cancer.

Cao WM, Gao Y, Yang HJ, Xie SN, Ding XW, Pan ZW, Ye WW, Wang XJ.

BMC Cancer. 2016 Feb 6;16:64. doi: 10.1186/s12885-016-2107-6.

PubMed [citation]

PMID:: 26852015
PMCID:: PMC4744435

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000549768.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1864 of the BRCA2 protein (p.Asp1864Asn). This variant is present in population databases (rs587781536, gnomAD 0.01%). This missense change has been observed in individual(s) with breast and/or ovarian cancer and in an individual with esophageal squamous cell carcinoma and esophageal squamous cell carcinoma (PMID: 22126563, 26852015, 27257965, 30415210, 30725392, 31161121, 31907386). ClinVar contains an entry for this variant (Variation ID: 141155). 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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