NM_000059.4(BRCA2):c.574_575del (p.Met192fs) AND Breast-ovarian cancer, familial, susceptibility to, 2

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Apr 22, 2016
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:: RCV000031574.20

Allele description [Variation Report for NM_000059.4(BRCA2):c.574_575del (p.Met192fs)]

NM_000059.4(BRCA2):c.574_575del (p.Met192fs)

Gene:

BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.574_575del (p.Met192fs)

Other names:

802_803delAT

HGVS:

NC_000013.10:g.32900691_32900692del
NC_000013.11:g.32326554AT[1]
NG_012772.3:g.16075AT[1]
NM_000059.4:c.574_575delMANE SELECT
NP_000050.3:p.Met192fs
LRG_293:g.16075AT[1]
NC_000013.10:g.32900691AT[1]
NC_000013.10:g.32900691_32900692del
NC_000013.10:g.32900693_32900694del
NC_000013.10:g.32900693_32900694delAT
NM_000059.3:c.574_575delAT
NM_000059.4:c.574_575del
U43746.1:n.802_803delAT
p.M192Vfs*13
p.M192VfsX13
p.Met192Valfs*13
p.Met192fs

Nucleotide change:

802delAT

Protein change:

M192fs

Links:

Breast Cancer Information Core (BIC) (BRCA2): 802&base_change=del AT; dbSNP: rs80359533

NCBI 1000 Genomes Browser:

rs80359533

Molecular consequence:

NM_000059.4:c.574_575del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000054180	Sharing Clinical Reports Project (SCRP)	no assertion criteria provided	Pathogenic (Jul 5, 2013)	germline	clinical testing
SCV000147183	Breast Cancer Information Core (BIC) (BRCA2)	no assertion criteria provided	Pathogenic (May 29, 2002)	germline, unknown	clinical testing
SCV000267733	Michigan Medical Genetics Laboratories, University of Michigan	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 21, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000282414	Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015))	Pathogenic (Apr 22, 2016)	germline	curation	ENIGMA BRCA1/2 Classification Criteria (2015), Citation Link,
SCV000327274	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,
SCV000489153	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Pathogenic (Aug 29, 2016)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20215541, 12960223, 24094589 Counsyl Autosomal Dominant Disease Classification criteria (2015), Citation Link,
SCV004846790	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 9, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 12672316, 21913181, 24094589, 24131973, 26681312, 31090900, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	7	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	25	not provided	108544	not provided	clinical testing, curation
not provided	germline	not provided	9	not provided	not provided	9	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
African American	not provided	yes	1	not provided	not provided	not provided	not provided	clinical testing
Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Native American	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
Native American, Central/Eastern European	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Native American, Western European, Irish	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
Western European	germline	yes	16	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.

Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA.

Clin Cancer Res. 2010 Mar 15;16(6):1957-67. doi: 10.1158/1078-0432.CCR-09-2564. Epub 2010 Mar 9.

PubMed [citation]

PMID:: 20215541

Sensitivity of BRCA1/2 mutation testing in 466 breast/ovarian cancer families.

Evans DG, Bulman M, Young K, Gokhale D, Lalloo F.

J Med Genet. 2003 Sep;40(9):e107. No abstract available.

PubMed [citation]

PMID:: 12960223
PMCID:: PMC1735589

See all PubMed Citations (9)

Details of each submission

From Sharing Clinical Reports Project (SCRP), SCV000054180.6

#	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	9	not provided	not provided		not provided	not provided	not provided	See 1

Co-occurrences

#	Zygosity	Alleles	Number of Observations
1	SingleHeterozygote	BRCA2:10153G>A (E3309K)	1

From Breast Cancer Information Core (BIC) (BRCA2), SCV000147183.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	not provided	not provided	clinical testing	not provided
2	African American	1	not provided	not provided	clinical testing	not provided
3	Central/Eastern European	1	not provided	not provided	clinical testing	not provided
4	Native American	3	not provided	not provided	clinical testing	not provided
5	Native American, Central/Eastern European	1	not provided	not provided	clinical testing	not provided
6	Native American, Western European, Irish	1	not provided	not provided	clinical testing	not provided
7	Western European	16	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		7	not provided	not provided	not provided
2	unknown	yes	not provided	not provided	not provided		1	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		3	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		16	not provided	not provided	not provided

From Michigan Medical Genetics Laboratories, University of Michigan, SCV000267733.1

#	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	yes	not provided	Blood	not provided		not provided	not provided	not provided	not provided

From Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA), SCV000282414.1

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

Description

Variant allele predicted to encode a truncated non-functional protein.

#	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, SCV000327274.4

#	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	25	not provided

From Counsyl, SCV000489153.2

#	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

From All of Us Research Program, National Institutes of Health, SCV004846790.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

This variant deletes 2 nucleotides in exon 7 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 800delAT in the literature. This variant is expected to result in an absent or non-functional protein product. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least six individuals affected with breast and/or ovarian cancer (PMID: 12672316, 21913181, 24094589, 24131973, 26681312, 31090900). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 26, 2024

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