NM_000059.4(BRCA2):c.3007C>G (p.His1003Asp) 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:: RCV000229829.8

Allele description [Variation Report for NM_000059.4(BRCA2):c.3007C>G (p.His1003Asp)]

NM_000059.4(BRCA2):c.3007C>G (p.His1003Asp)

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.3007C>G (p.His1003Asp)

HGVS:

NC_000013.11:g.32337362C>G
NG_012772.3:g.26883C>G
NM_000059.4:c.3007C>GMANE SELECT
NP_000050.2:p.His1003Asp
NP_000050.3:p.His1003Asp
LRG_293t1:c.3007C>G
LRG_293:g.26883C>G
LRG_293p1:p.His1003Asp
NC_000013.10:g.32911499C>G
NM_000059.3:c.3007C>G

Protein change:

H1003D

Links:

dbSNP: rs878853565

NCBI 1000 Genomes Browser:

rs878853565

Molecular consequence:

NM_000059.4:c.3007C>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
SCV000283201	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19499246, 30415210, 33078592, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000283201

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 27, 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

BRCA1 and BRCA2 germline mutations in Korean ovarian cancer patients.

Lim MC, Kang S, Seo SS, Kong SY, Lee BY, Lee SK, Park SY.

J Cancer Res Clin Oncol. 2009 Nov;135(11):1593-9. doi: 10.1007/s00432-009-0607-3. Epub 2009 Jun 5.

PubMed [citation]

PMID:: 19499246

Reclassification of BRCA1 and BRCA2 variants of uncertain significance: a multifactorial analysis of multicentre prospective cohort.

Lee JS, Oh S, Park SK, Lee MH, Lee JW, Kim SW, Son BH, Noh DY, Lee JE, Park HL, Kim MJ, Cho SI, Lee YK, Park SS, Seong MW.

J Med Genet. 2018 Dec;55(12):794-802. doi: 10.1136/jmedgenet-2018-105565. Epub 2018 Nov 10.

PubMed [citation]

PMID:: 30415210

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000283201.5

#	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: 236845). This missense change has been observed in individual(s) with breast and ovarian cancer (PMID: 19499246, 30415210, 33078592). This variant is present in population databases (no rsID available, gnomAD 0.06%). This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 1003 of the BRCA2 protein (p.His1003Asp).

#	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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