NM_000059.4(BRCA2):c.3007C>G (p.His1003Asp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Mar 23, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000509749.12

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 cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000607812	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 13, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000903430	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 17, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003850309	University of Washington Department of Laboratory Medicine, University of Washington	criteria provided, single submitter (Dines et al. (Genet Med. 2020))	Likely benign (Mar 23, 2023)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000607812

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 13, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV000903430

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jan 17, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003850309

University of Washington Department of Laboratory Medicine, University of Washington

criteria provided, single submitter

(Dines et al. (Genet Med. 2020))

Likely benign
(Mar 23, 2023)

germline

curation

PubMed (1)
[See all records that cite this PMID]

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, curation

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000607812.5

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

Description

The p.H1003D variant (also known as c.3007C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 3007. The histidine at codon 1003 is replaced by aspartic acid, an amino acid with similar properties. In one study, this alteration was identified in 1/337 Korean ovarian cancer patients (Lim MC et al. J. Cancer Res. Clin. Oncol., 2009 Nov;135:1593-9). This amino acid position is highly conserved through the hedgehog, but is not conserved in lower species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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

From Color Diagnostics, LLC DBA Color Health, SCV000903430.2

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

#	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

From University of Washington Department of Laboratory Medicine, University of Washington, SCV003850309.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

#	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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