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NM_000465.4(BARD1):c.1639G>T (p.Glu547Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Aug 6, 2020
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:
RCV000213181.8

Allele description [Variation Report for NM_000465.4(BARD1):c.1639G>T (p.Glu547Ter)]

NM_000465.4(BARD1):c.1639G>T (p.Glu547Ter)

Gene:
BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_000465.4(BARD1):c.1639G>T (p.Glu547Ter)
HGVS:
  • NC_000002.12:g.214752485C>A
  • NG_012047.3:g.62227G>T
  • NM_000465.4:c.1639G>TMANE SELECT
  • NM_001282543.2:c.1582G>T
  • NM_001282545.2:c.286G>T
  • NM_001282548.2:c.229G>T
  • NM_001282549.2:c.365-21977G>T
  • NP_000456.2:p.Glu547Ter
  • NP_001269472.1:p.Glu528Ter
  • NP_001269474.1:p.Glu96Ter
  • NP_001269477.1:p.Glu77Ter
  • LRG_297t1:c.1639G>T
  • LRG_297:g.62227G>T
  • LRG_297p1:p.Glu547Ter
  • NC_000002.11:g.215617209C>A
  • NG_012047.2:g.62220G>T
  • NM_000465.2:c.1639G>T
  • NR_104212.2:n.1604G>T
  • NR_104215.2:n.1547G>T
  • NR_104216.2:n.803G>T
Protein change:
E528*
Links:
dbSNP: rs876658429
NCBI 1000 Genomes Browser:
rs876658429
Molecular consequence:
  • NM_001282549.2:c.365-21977G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NR_104212.2:n.1604G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104215.2:n.1547G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104216.2:n.803G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000465.4:c.1639G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001282543.2:c.1582G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001282545.2:c.286G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001282548.2:c.229G>T - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000273618Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Aug 6, 2020) 		germlineclinical testing

Citation Link,

SCV001350794Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Aug 12, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Ambry Genetics, SCV000273618.7

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

Description

The p.E547* pathogenic mutation (also known as c.1639G>T), located in coding exon 7 of the BARD1 gene, results from a G to T substitution at nucleotide position 1639. This changes the amino acid from a glutamic acid to a stop codon within coding exon 7. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

From Color Diagnostics, LLC DBA Color Health, SCV001350794.2

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

Description

This variant changes 1 nucleotide in exon 7 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease. Based on available evidence, this variant is classified as Pathogenic.

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

Last Updated: May 1, 2024