NM_000059.3(BRCA2):c.1114A>C (p.Asn372His) AND Breast-ovarian cancer, familial 2

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

Germline classification:: conflicting data from submitters (2 submissions)
Last evaluated:: Jan 2, 2014
Review status:: 2 stars out of maximum of 4 stars
conflicting data from submitters (classified by multiple submitters)

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:: RCV000009916.3

Allele description

NM_000059.3(BRCA2):c.1114A>C (p.Asn372His)

Gene:

BRCA2:breast cancer 2, early onset [Gene - OMIM]

Variant type:

single nucleotide variant

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.3(BRCA2):c.1114A>C (p.Asn372His)

HGVS:

NC_000013.11:g.32332592A>C
NG_012772.3:g.22113A>C
NM_000059.3:c.1114A>C
NP_000050.2:p.Asn372His
LRG_293t1:c.1114A>C
LRG_293:g.22113A>C
LRG_293p1:p.Asn372His
NC_000013.10:g.32906729A>C
p.N372H

Protein change:

N372H; ASN372HIS

Links:

OMIM: 600185.0013; dbSNP: rs144848

GMAF:

0.2494(C), 144848

NCBI 1000 Genomes Browser:

rs144848

Allele Frequency:

0.2332, GO-ESP

Molecular consequence:

NM_000059.3:c.1114A>C - missense variant - [Sequence Ontology: SO:0001583]
U43746.1:c.1114C= - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:

Breast-ovarian cancer, familial 2 (BROVCA2)

Synonyms:

BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 2; Breast cancer, familial 2; See all synonyms [MedGen]

Identifiers:

MedGen: C2675520; Orphanet: 145; OMIM: 612555

Age of onset:

Variable

Prevalence:

1-5 / 10 000 Orphanet: 145
Hereditary breast and ovarian cancer (HBOC) resulting from mutations in BRCA1 and BRCA2 is the most common form of both hereditary breast and ovarian cancers and occurs in all ethnic and racial populations. The overall prevalence of BRCA1/2 mutations is estimated to be from 1:400 to 1:800 [Ford et al 1994, Claus et al 1996, Whittemore et al 1997], but varies depending on ethnicity. http://www.ncbi.nlm.nih.gov/books/NBK1247/

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000030137	OMIM		Pathogenic (Nov 9, 2012)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 11062481, 15235023
SCV000154058	Counsyl	classified by single submitter	Benign (Jan 2, 2014)	unknown	literature only

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000030137

OMIM

Pathogenic
(Nov 9, 2012)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000154058

Counsyl

classified by single submitter

Benign
(Jan 2, 2014)

unknown

literature only

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability.

Healey CS, Dunning AM, Teare MD, Chase D, Parker L, Burn J, Chang-Claude J, Mannermaa A, Kataja V, Huntsman DG, Pharoah PD, Luben RN, Easton DF, Ponder BA.

Nat Genet. 2000 Nov;26(3):362-4.

PubMed [citation]

PMID:: 11062481

Heterozygote excess is repeatedly observed in females at the BRCA2 locus N372H.

Teare MD, Cox A, Shorto J, Anderson C, Bishop DT, Cannings C.

J Med Genet. 2004 Jul;41(7):523-8. No abstract available.

PubMed [citation]

PMID:: 15235023
PMCID:: PMC1735827

Details of each submission

From OMIM, SCV000030137.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

Healey et al. (2000) described a polymorphism of the BRCA2 gene, asn372 to his (N372H), located in exon 10 and associated not only with an increased risk of breast cancer (612555) but also with an effect on prenatal viability with increased fitness of males and decreased fitness of females. The rarer allele (372H) had a frequency of 0.221 in Finnish, 0.285 in German, and a frequency intermediate between these 2 in British populations.

Using a mathematical model to analyze the BRCA2 N372H polymorphism data reported by Healey et al. (2000) as well as data from 8 other populations, Teare et al. (2004) found significant evidence consistent with a heterozygote advantage in females, but no evidence of genotype-specific selection in males.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Counsyl, SCV000154058.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	literature only	not provided

Description

High frequency in a 1kG or ESP population: 28.6 %.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 14, 2015

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