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NM_000059.4(BRCA2):c.9777del (p.Ile3259fs) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 1, 2023
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:
RCV003307568.9

Allele description [Variation Report for NM_000059.4(BRCA2):c.9777del (p.Ile3259fs)]

NM_000059.4(BRCA2):c.9777del (p.Ile3259fs)

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.9777del (p.Ile3259fs)
HGVS:
  • NC_000013.11:g.32398290del
  • NG_012772.3:g.87811del
  • NM_000059.4:c.9777delMANE SELECT
  • NM_000059.4:c.9777delT
  • NP_000050.3:p.Ile3259fs
  • LRG_293:g.87811del
  • NC_000013.10:g.32972426del
  • NC_000013.10:g.32972427del
  • NC_000013.10:g.32972427delT
  • NM_000059.3:c.9777del
  • NM_000059.3:c.9777delT
  • NM_000059.4:c.9777del
  • p.Ile3259MetfsX16
Protein change:
I3259fs
Links:
dbSNP: rs1593201815
NCBI 1000 Genomes Browser:
rs1593201815
Molecular consequence:
  • NM_000059.4:c.9777del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004005441Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(May 1, 2023) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Exome Sequencing-Based Screening for BRCA1/2 Expected Pathogenic Variants Among Adult Biobank Participants.

Manickam K, Buchanan AH, Schwartz MLB, Hallquist MLG, Williams JL, Rahm AK, Rocha H, Savatt JM, Evans AE, Butry LM, Lazzeri AL, Lindbuchler DM, Flansburg CN, Leeming R, Vogel VG, Lebo MS, Mason-Suares HM, Hoskinson DC, Abul-Husn NS, Dewey FE, Overton JD, Reid JG, et al.

JAMA Netw Open. 2018 Sep 7;1(5):e182140. doi: 10.1001/jamanetworkopen.2018.2140.

PubMed [citation]
PMID:
30646163
PMCID:
PMC6324494

Details of each submission

From Ambry Genetics, SCV004005441.2

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

Description

The c.9777delT pathogenic mutation, located in coding exon 26 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 9777, causing a translational frameshift with a predicted alternate stop codon (p.I3259Mfs*16). This alteration has been reported in an unaffected individual from an unselected population cohort (Manickam K et al. JAMA Netw Open, 2018 Sep;1:e182140). This alteration occurs at the 3' terminus of theBRCA2 gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 160 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Nov 3, 2024