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NM_000059.3(BRCA2):c.1796_1800delCTTAT (p.Ser599Terfs) AND Hereditary breast and ovarian cancer syndrome

Germline classification:
Pathogenic (3 submissions)
Last evaluated:
Jan 10, 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:
RCV000168232.5

Allele description

NM_000059.3(BRCA2):c.1796_1800delCTTAT (p.Ser599Terfs)

Gene:
BRCA2:BRCA2, DNA repair associated [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.1796_1800delCTTAT (p.Ser599Terfs)
Other names:
2022del5; 2024_2028delCTTAT
HGVS:
  • NC_000013.11:g.32333274_32333278delCTTAT
  • NG_012772.3:g.22795_22799delCTTAT
  • NM_000059.3:c.1796_1800delCTTAT
  • NP_000050.2:p.Ser599Terfs
  • LRG_293t1:c.1796_1800delCTTAT
  • LRG_293:g.22795_22799delCTTAT
  • LRG_293p1:p.Ser599Terfs
  • NC_000013.10:g.32907411_32907415delCTTAT
  • NM_000059.3:c.1796_1800del
  • NM_000059.3:c.1796_1800del5
  • U43746.1:c.1796_1800delTTTAT
  • U43746.1:n.2022_2026delATTTT
  • U43746.1:n.2024_2028delTTTAT
  • p.S599*
  • p.S599X
  • p.Ser599*
Nucleotide change:
2024del5
Links:
Breast Cancer Information Core (BIC) (BRCA2): 2022&base_change=del ATTTT; Breast Cancer Information Core (BIC) (BRCA2): 2024&base_change=del TTTAT; dbSNP: rs276174813
NCBI 1000 Genomes Browser:
rs276174813
Molecular consequence:
  • NM_000059.3:c.1796_1800delCTTAT - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary breast and ovarian cancer syndrome (HBOC)
Synonyms:
Hereditary breast and ovarian cancer
Identifiers:
MeSH: D061325; MedGen: C0677776; Orphanet: 145; OMIM: PS604370

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000071900Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 19, 2016)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV000591768Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Apr 8, 2015)
germlineclinical testing

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

SCV000694563Integrated Genetics/Laboratory Corporation of America
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Pathogenic
(Jan 10, 2017)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene.

Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BA, Stratton MR, Easton D.

Nat Genet. 1997 Jan;15(1):103-5.

PubMed [citation]
PMID:
8988179
See all PubMed Citations (9)

Details of each submission

From Invitae, SCV000071900.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change deletes 5 nucleotides from exon 10 of the BRCA2 mRNA (c.1796_1800delCTTAT). This creates a premature translational stop signal (p.Ser599*) and is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic. This variant has been reported in individuals affected with breast cancer (PMID: 22009639, 8988179, 24549055, 22085629, 22798144). This variant is also known as c.1796delCTTAT and 2024del5 in the literature. For these reasons, this sequence change has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591768.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Integrated Genetics/Laboratory Corporation of America, SCV000694563.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: The BRCA2 c.1796_1800delCTTAT (p.Ser599Terfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs, or ESP) and has been reported in multiple affected individuals via publications. In addition, multiple clinical diagnostic laboratories/databases cite the variant as "pathogenic." Therefore, the variant of interest has been classified as "Pathogenic."

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 30, 2018