NM_000059.3(BRCA2):c.235A>G (p.Ile79Val) AND Malignant tumor of breast

Clinical significance:Uncertain significance

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000500366.2

Allele description [Variation Report for NM_000059.3(BRCA2):c.235A>G (p.Ile79Val)]

NM_000059.3(BRCA2):c.235A>G (p.Ile79Val)

Gene:
BRCA2:BRCA2 DNA repair associated [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
13q13.1
Genomic location:
Preferred name:
NM_000059.3(BRCA2):c.235A>G (p.Ile79Val)
HGVS:
  • NC_000013.11:g.32319244A>G
  • NG_012772.3:g.8765A>G
  • NG_017006.2:g.1120T>C
  • NM_000059.3:c.235A>G
  • NP_000050.2:p.Ile79Val
  • LRG_293t1:c.235A>G
  • LRG_293:g.8765A>G
  • LRG_293p1:p.Ile79Val
  • NC_000013.10:g.32893381A>G
  • U43746.1:n.463A>G
Protein change:
I79V
Links:
dbSNP: rs80358502
NCBI 1000 Genomes Browser:
rs80358502
Molecular consequence:
  • NM_000059.3:c.235A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Malignant tumor of breast
Synonyms:
Breast cancer; Malignant breast neoplasm
Identifiers:
MONDO: MONDO:0007254; MedGen: C0006142

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000591666Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes1not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000591666.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided

Description

The BRCA2 p.Ile79Val variant was not identified in the literature, nor was it identified in the NHLBI Exome Sequencing Project (Exome Variant Server), Fanconi’s Anemia Mutation Database (LOVD), COSMIC, GeneInsight COGR, MutDB or ARUP . This variant was identified in the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) in 3 of 121174 chromosomes (frequency: 2.05x10-5); all 3 were found in 6614 alleles (frequency: 4.54x10-4) in the European Finnish population, increasing the likelihood that this may be a low frequency benign variant. The variant was not identified in populations of South Asians, European (Non-Finnish), East Asian, African, Latino, and other individuals.The variant was also identified in dbSNP (ID: rs80358502 “With Uncertain significance allele”. The ClinVar database classified the variant as an uncertain significance variant by the Sharing Clinical Reports Project, derived from Myriad reports), as uncertain significance by BIC and classification not provided by Invitae. The variant was identified in BIC database (1x with Unknown clinical importance), and BRCA Share UMD (1x as an unknown variant). The p.Ile79 residue is not conserved in mammals and the variant amino acid Valine (Val) is present in Cows and African clawed frogs, increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. The c.235A>G variant occurs outside of the splicing consensus sequence and 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict the creation of a cryptic splice acceptor site. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as a variant of unknown significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 6, 2021

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