NM_000465.3(BARD1):c.2300_2301delTG (p.Val767Aspfs) AND Familial cancer of breast

Clinical significance:Uncertain significance (Last evaluated: Aug 18, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000476131.1

Allele description

NM_000465.3(BARD1):c.2300_2301delTG (p.Val767Aspfs)

Gene:
BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_000465.3(BARD1):c.2300_2301delTG (p.Val767Aspfs)
HGVS:
  • NC_000002.12:g.214728709_214728710delCA
  • NG_012047.2:g.85995_85996delTG
  • NM_000465.3:c.2300_2301delTG
  • NP_000456.2:p.Val767Aspfs
  • NC_000002.11:g.215593433_215593434delCA
  • NM_000465.2:c.2300_2301delTG
  • NR_104212.1:n.2293_2294delTG
Links:
dbSNP: rs750413473
NCBI 1000 Genomes Browser:
rs750413473
Allele Frequency:
0.00006(-)
Molecular consequence:
  • NM_000465.3:c.2300_2301delTG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_104212.1:n.2293_2294delTG - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial cancer of breast
Synonyms:
CHEK2-Related Breast Cancer
Identifiers:
MedGen: C0346153; OMIM: 114480

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000545582Invitaecriteria provided, single submitter
Uncertain significance
(Aug 18, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Invitae, SCV000545582.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This sequence change deletes 2 nucleotides from exon 11 of the BARD1 mRNA (c.2300_2301delTG), causing a frameshift at codon 767. This creates a premature translational stop signal in the last exon of the BARD1 mRNA (p.Val767Aspfs*4). While premature stop is not anticipated to cause mRNA decay, it is expected to result in a protein missing the last 10 amino acids of the BARD1 protein. This variant is present in population databases (rs750413473, ExAC 0.02%). This variant has been reported in an individual affected with breast cancer (PMID: 25452441), and in an individual affected with ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 230523). Experimental studies have not been reported for this truncating variant and it is currently unknown if the last 10 amino acids of the BARD1 protein are critical for its function. In summary, this variant is a rare truncation with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Apr 17, 2017