NM_007299.4(BRCA1):c.1965+1G>A AND Breast-ovarian cancer, familial 1

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

Germline classification:: Pathogenic (8 submissions)
Last evaluated:: Aug 10, 2015
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000031235.8

Allele description

NM_007299.4(BRCA1):c.1965+1G>A

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

17q21.31

Genomic location:

Preferred name:

NM_007299.4(BRCA1):c.1965+1G>A

Other names:

IVS19+1 G>A

HGVS:

NC_000017.11:g.43057051C>T
NG_005905.2:g.160933G>A
NM_007294.3:c.5277+1G>A
NM_007297.4:c.5136+1G>A
NM_007298.3:c.1965+1G>A
NM_007299.4:c.1965+1G>A
NM_007300.4:c.5340+1G>A
LRG_292t1:c.5277+1G>A
LRG_292:g.160933G>A
NC_000017.10:g.41209068C>T
NM_007297.3:c.5136+1G>A
NM_007299.3:c.1965+1G>A
NM_007300.3:c.5340+1G>A
U14680.1:n.5396+1G>A

Nucleotide change:

IVS20+1G>A

Links:

BRCA1-HCI: BRCA1_00146; Breast Cancer Information Core (BIC) (BRCA1): 5396+1&base_change=G to A; dbSNP: rs80358150

Molecular consequence:

NM_007294.3:c.5277+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007297.4:c.5136+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007298.3:c.1965+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007299.4:c.1965+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_007300.4:c.5340+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Functional consequence:

sequence_variant_affecting_splicing [Sequence Ontology: SO:1000071] - Comment(s)

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial 1 (BROVCA1)
Synonyms:: BREAST-OVARIAN CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; OVARIAN CANCER, SUSCEPTIBILITY TO; BREAST CANCER, FAMILIAL, SUSCEPTIBILITY TO, 1; See all synonyms [MedGen]
Identifiers:: MedGen: C2676676; Orphanet: 145; OMIM: 604370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000053836	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (May 2, 2012)	germline	clinical testing
SCV000145422	Breast Cancer Information Core (BIC) (BRCA1)	no assertion criteria provided	Pathogenic (Dec 30, 1999)	germline	clinical testing
SCV000220602	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Aug 19, 2014)	unknown	literature only	PubMed (8) [See all records that cite these PMIDs] 24667779, 17924331, 11149413, 12955716, 21990134, 20215541, 23348723, 16211554 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV000244394	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Aug 10, 2015)	germline	curation	PubMed (1) [See all records that cite this PMID] ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000326234	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016)	Pathogenic (Oct 2, 2015)	germline	clinical testing	CIMBA_Mutation_Classification_guidelines_May16.pdf, Citation Link,
SCV000733590	Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV000743373	Genome Diagnostics Laboratory,University Medical Center Utrecht - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Oct 8, 2014)	germline	clinical testing	Citation Link,
SCV000744588	DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus	criteria provided, single submitter (ACGS Guidelines, 2013)	Pathogenic (Sep 21, 2015)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	80	not provided	not provided	not provided	clinical testing, curation
not provided	germline	yes	21	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	not provided	8	not provided	not provided	8	not provided	clinical testing
Caucasian	germline	yes	18	not provided	not provided	not provided	not provided	clinical testing
Dutch	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Latin American, Caribbean	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	7	not provided	not provided	not provided	not provided	clinical testing
Western Europeanan, Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Functional characterization of BRCA1 gene variants by mini-gene splicing assay.

Steffensen AY, Dandanell M, Jønson L, Ejlertsen B, Gerdes AM, Nielsen FC, Hansen Tv.

Eur J Hum Genet. 2014 Dec;22(12):1362-8. doi: 10.1038/ejhg.2014.40. Epub 2014 Mar 26.

PubMed [citation]

PMID:: 24667779
PMCID:: PMC4231409

A systematic genetic assessment of 1,433 sequence variants of unknown clinical significance in the BRCA1 and BRCA2 breast cancer-predisposition genes.

Easton DF, Deffenbaugh AM, Pruss D, Frye C, Wenstrup RJ, Allen-Brady K, Tavtigian SV, Monteiro AN, Iversen ES, Couch FJ, Goldgar DE.

Am J Hum Genet. 2007 Nov;81(5):873-83. Epub 2007 Sep 6.

PubMed [citation]

PMID:: 17924331
PMCID:: PMC2265654

See all PubMed Citations (8)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000053836.6

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	8	not provided	not provided		not provided	not provided	not provided	not provided

From Breast Cancer Information Core (BIC) (BRCA1), SCV000145422.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	10	not provided	not provided	clinical testing	not provided
2	not provided	10	not provided	not provided	clinical testing	not provided
3	not provided	1	not provided	not provided	clinical testing	not provided
4	Caucasian	17	not provided	not provided	clinical testing	not provided
5	Caucasian	1	not provided	not provided	clinical testing	not provided
6	Dutch	1	not provided	not provided	clinical testing	not provided
7	Latin American, Caribbean	1	not provided	not provided	clinical testing	not provided
8	Western European	7	not provided	not provided	clinical testing	not provided
9	Western Europeanan, Central/Eastern European	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		10	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		10	not provided	not provided	not provided
3	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		17	not provided	not provided	not provided
5	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
6	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
7	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
8	germline	yes	not provided	not provided	not provided		7	not provided	not provided	not provided
9	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Counsyl, SCV000220602.1

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

#	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

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000244394.1

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

Description

IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 5 based on posterior probability = 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 Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000326234.3

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

#	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	80	not provided

From Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen - VKGL Data-share Consensus, SCV000733590.1

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

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

From Genome Diagnostics Laboratory,University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743373.1

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

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

From DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center - VKGL Data-share Consensus, SCV000744588.1

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

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

Last Updated: Apr 15, 2020

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