NM_000059.4(BRCA2):c.8487+2T>C AND Hereditary breast ovarian cancer syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 12, 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:: RCV002518791.10

Allele description [Variation Report for NM_000059.4(BRCA2):c.8487+2T>C]

NM_000059.4(BRCA2):c.8487+2T>C

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.8487+2T>C

HGVS:

NC_000013.11:g.32370559T>C
NG_012772.3:g.60080T>C
NM_000059.4:c.8487+2T>CMANE SELECT
NM_001406719.1:c.8391+2T>C
NM_001406720.1:c.8487+2T>C
NM_001406721.1:c.3555+2T>C
NM_001406722.1:c.2070+2T>C
LRG_293t1:c.8487+2T>C
LRG_293:g.60080T>C
NC_000013.10:g.32944696T>C
NM_000059.3:c.8487+2T>C

Links:

dbSNP: rs886040944

NCBI 1000 Genomes Browser:

rs886040944

Molecular consequence:

NM_000059.4:c.8487+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406719.1:c.8391+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406720.1:c.8487+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406721.1:c.3555+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406722.1:c.2070+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV003472609	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 12, 2022)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 30287823, 12442275, 15889636, 16030099, 23108138, 23233716, 25085752, 25777348, 12606139, 16619214, 22632462, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003472609

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 12, 2022)

germline

clinical testing

PubMed (12)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico.

Ruiz-Flores P, Sinilnikova OM, Badzioch M, Calderon-Garcidueñas AL, Chopin S, Fabrice O, González-Guerrero JF, Szabo C, Lenoir G, Goldgar DE, Barrera-Saldaña HA.

Hum Mutat. 2002 Dec;20(6):474-5.

PubMed [citation]

PMID:: 12442275

See all PubMed Citations (12)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003472609.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 19 of the BRCA2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. Disruption of this splice site has been observed in individual(s) with breast cancer (PMID: 30287823). For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the BRCA2 protein in which other variant(s) (p.Gly2793Arg) have been determined to be pathogenic (PMID: 12442275, 15889636, 16030099, 23108138, 23233716, 25085752, 25777348). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Studies have shown that disruption of this splice site results in skipping of exon 19, but is expected to preserve the integrity of the reading-frame (PMID: 12606139, 16619214, 22632462). ClinVar contains an entry for this variant (Variation ID: 267697).

#	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

ClinVar

Relating variation to medicine