NM_007294.3(BRCA1):c.213-11T>G AND Hereditary breast and ovarian cancer syndrome

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 11, 2017
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000047725.7

Allele description

NM_007294.3(BRCA1):c.213-11T>G

Gene:

BRCA1:BRCA1, DNA repair associated [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007294.3(BRCA1):c.213-11T>G

Other names:

IVS4-11 T>G

HGVS:

NC_000017.11:g.43104967A>C
NG_005905.2:g.113017T>G
NM_007294.3:c.213-11T>G
LRG_292t1:c.213-11T>G
LRG_292:g.113017T>G
NC_000017.10:g.41256984A>C
U14680.1:n.332-11T>G

Nucleotide change:

IVS5-11T>G

Links:

Breast Cancer Information Core (BIC) (BRCA1): 332-11&base_change=T to G; dbSNP: rs80358061

NCBI 1000 Genomes Browser:

rs80358061

Allele Frequency:

0.00001(C)

Molecular consequence:

NM_007294.3:c.213-11T>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:: Hereditary breast and ovarian cancer
Identifiers:: MedGen: C0677776; Orphanet: 145
Prevalence:: http://www.ncbi.nlm.nih.gov/books/NBK1247/ https://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
SCV000075738	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 11, 2017)	germline	clinical testing	Citation Link,
SCV000219187	Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG guidelines, 2007)	Pathogenic (Aug 10, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000075738

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 11, 2017)

germline

clinical testing

Citation Link,

SCV000219187

Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG guidelines, 2007)

Pathogenic
(Aug 10, 2012)

germline

clinical testing

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	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

ACMG recommendations for standards for interpretation and reporting of sequence variations: Revisions 2007.

Richards CS, Bale S, Bellissimo DB, Das S, Grody WW, Hegde MR, Lyon E, Ward BE; Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee..

Genet Med. 2008 Apr;10(4):294-300. doi: 10.1097/GIM.0b013e31816b5cae.

PubMed [citation]

PMID:: 18414213

Details of each submission

From Invitae, SCV000075738.8

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

Description

This sequence change falls in intron 4 of the BRCA1 mRNA. It does not directly change the encoded amino acid sequence of the BRCA1 protein. This variant is present in population databases (rs80358061, ExAC 0.002%). This variant was reported to segregate with disease in a large family affected with breast and ovarian cancer (PMID: 7894493), and has been observed in many unrelated individuals with breast and/or ovarian cancer (PMID: 18284688, 21993507, 25452441, 10923033, 22144684). In the literature, this variant is also known as c.332-11T>G and IVS5-11T>G. ClinVar contains an entry for this variant (Variation ID: 37449). Experimental studies have demonstrated that this variant weakens the consensus acceptor splice site in intron 4, which leads to the use of a cryptic acceptor splice site 59 nucleotides upstream of the 5' end of exon 5 (PMID: 18424508, 23451180). This is expected to result in a frameshift in the BRCA1 mRNA and an absent or truncated protein. For these reasons, this variant has been classified as Pathogenic.

#	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 Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario, SCV000219187.2

#	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	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 5, 2017

ClinVar

Relating variation to medicine