NM_000059.4(BRCA2):c.1909+1G>A AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 23, 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:: RCV000238861.14

Allele description [Variation Report for NM_000059.4(BRCA2):c.1909+1G>A]

NM_000059.4(BRCA2):c.1909+1G>A

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.1909+1G>A

HGVS:

NC_000013.11:g.32333388G>A
NG_012772.3:g.22909G>A
NM_000059.4:c.1909+1G>AMANE SELECT
NM_001406719.1:c.1909+1G>A
NM_001406720.1:c.1909+1G>A
NM_001406721.1:c.1909+1G>A
NM_001406722.1:c.424+2358G>A
LRG_293t1:c.1909+1G>A
LRG_293:g.22909G>A
NC_000013.10:g.32907525G>A
NM_000059.3:c.1909+1G>A

Links:

dbSNP: rs587781629

NCBI 1000 Genomes Browser:

rs587781629

Molecular consequence:

NM_001406722.1:c.424+2358G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000059.4:c.1909+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.1909+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.1909+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.1909+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Name:: Breast-ovarian cancer, familial, susceptibility to, 2 (BROVCA2)
Synonyms:: Breast-ovarian cancer, familial 2
Identifiers:: MONDO: MONDO:0012933; MedGen: C2675520; Orphanet: 145; OMIM: 612555

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000326635	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,
SCV000591779	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Pathogenic	unknown	clinical testing
SCV000785268	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Jun 23, 2017)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26296696, 26681678, 26845104 Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000326635

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,

SCV000591779

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Pathogenic

unknown

clinical testing

SCV000785268

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Dominant Disease Classification criteria (2015))

Pathogenic
(Jun 23, 2017)

unknown

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	1	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening.

Frey MK, Kim SH, Bassett RY, Martineau J, Dalton E, Chern JY, Blank SV.

Gynecol Oncol. 2015 Nov;139(2):211-5. doi: 10.1016/j.ygyno.2015.08.006. Epub 2015 Aug 18.

PubMed [citation]

PMID:: 26296696

Prospective phase II trial of trabectedin in BRCA-mutated and/or BRCAness phenotype recurrent ovarian cancer patients: the MITO 15 trial.

Lorusso D, Scambia G, Pignata S, Sorio R, Amadio G, Lepori S, Mosconi A, Pisano C, Mangili G, Maltese G, Sabbatini R, Artioli G, Gamucci T, Di Napoli M, Capoluongo E, Ludovini V, Raspagliesi F, Ferrandina G.

Ann Oncol. 2016 Mar;27(3):487-93. doi: 10.1093/annonc/mdv608. Epub 2015 Dec 17.

PubMed [citation]

PMID:: 26681678

See all PubMed Citations (3)

Details of each submission

From Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge, SCV000326635.4

#	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	1	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591779.2

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

Description

The BRCA2 c.1909+1G>A variant was not identified in the literature, but was identified in the UMD (2X as a causal variant). The c.1909+1G>A variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, HumanSpliceFinder) predict a difference in splicing, with an abolishment of the 5' slice donor site in the mutated sequence. In summary, based on the above information, this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic.

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

From Counsyl, SCV000785268.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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: Oct 26, 2024

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