NM_000059.4(BRCA2):c.2595del (p.Glu866fs) AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 26, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000496328.15

Allele description [Variation Report for NM_000059.4(BRCA2):c.2595del (p.Glu866fs)]

NM_000059.4(BRCA2):c.2595del (p.Glu866fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

13q13.1

Genomic location:

Preferred name:

NM_000059.4(BRCA2):c.2595del (p.Glu866fs)

Other names:

2823delA

HGVS:

NC_000013.10:g.32911086del
NC_000013.11:g.32336950del
NG_012772.3:g.26471del
NM_000059.4:c.2595delMANE SELECT
NM_000059.4:c.2595delA
NP_000050.3:p.Glu866fs
LRG_293:g.26471del
NC_000013.10:g.32911086del
NC_000013.10:g.32911087del
NC_000013.10:g.32911087delA
NM_000059.3:c.2595delA
U43746.1:n.2823delA

Links:

Breast Cancer Information Core (BIC) (BRCA2): 2823&base_change=del A; dbSNP: rs483353111

NCBI 1000 Genomes Browser:

rs483353111

Molecular consequence:

NM_000059.4:c.2595del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Hereditary breast ovarian cancer syndrome
Synonyms:: Hereditary breast and ovarian cancer syndrome; Hereditary breast and ovarian cancer; Hereditary breast and ovarian cancer syndrome (HBOC); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0003582; MeSH: D061325; MedGen: C0677776; Orphanet: 145

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000587638	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)	no assertion criteria provided	Pathogenic (Jan 31, 2014)	germline	research
SCV002246446	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 26, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 26187060, 28993434, 30702160, 20104584, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000587638

Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR)

no assertion criteria provided

Pathogenic
(Jan 31, 2014)

germline

research

SCV002246446

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 26, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Comprehensive spectrum of BRCA1 and BRCA2 deleterious mutations in breast cancer in Asian countries.

Kwong A, Shin VY, Ho JC, Kang E, Nakamura S, Teo SH, Lee AS, Sng JH, Ginsburg OM, Kurian AW, Weitzel JN, Siu MT, Law FB, Chan TL, Narod SA, Ford JM, Ma ES, Kim SW.

J Med Genet. 2016 Jan;53(1):15-23. doi: 10.1136/jmedgenet-2015-103132. Epub 2015 Jul 17. Review.

PubMed [citation]

PMID:: 26187060
PMCID:: PMC4681590

Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.

Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, Lee DS, Lee SY, Yoon SY, Lim J, Lau SY, Decker B, Pooley K, Dorling L, Luccarini C, Baynes C, Conroy DM, Harrington P, Simard J, Yip CH, Mohd Taib NA, Ho WK, et al.

J Med Genet. 2018 Feb;55(2):97-103. doi: 10.1136/jmedgenet-2017-104947. Epub 2017 Oct 9.

PubMed [citation]

PMID:: 28993434
PMCID:: PMC5800345

See all PubMed Citations (5)

Details of each submission

From Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto - The Canadian Open Genetics Repository (COGR), SCV000587638.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002246446.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 125988). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 26187060, 28993434, 30702160). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu866Lysfs*8) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).

#	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

Last Updated: Nov 3, 2024

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