NM_000465.4(BARD1):c.860A>T (p.Glu287Val) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 2, 2020
Review status:: criteria provided, conflicting classifications

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:: RCV001181265.6

Allele description [Variation Report for NM_000465.4(BARD1):c.860A>T (p.Glu287Val)]

NM_000465.4(BARD1):c.860A>T (p.Glu287Val)

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.860A>T (p.Glu287Val)

HGVS:

NC_000002.12:g.214781014T>A
NG_012047.3:g.33698A>T
NM_000465.4:c.860A>TMANE SELECT
NM_001282543.2:c.803A>T
NM_001282545.2:c.215+16047A>T
NM_001282548.2:c.158+28398A>T
NM_001282549.2:c.364+11283A>T
NP_000456.2:p.Glu287Val
NP_001269472.1:p.Glu268Val
LRG_297t1:c.860A>T
LRG_297:g.33698A>T
LRG_297p1:p.Glu287Val
NC_000002.11:g.215645738T>A
NG_012047.2:g.33691A>T
NM_000465.2:c.860A>T
NR_104212.2:n.825A>T
NR_104215.2:n.768A>T

Protein change:

E268V

Links:

dbSNP: rs1197692311

NCBI 1000 Genomes Browser:

rs1197692311

Molecular consequence:

NM_001282545.2:c.215+16047A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+28398A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+11283A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000465.4:c.860A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.803A>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.825A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.768A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001346366	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jan 2, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002676389	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Oct 21, 2015)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001346366

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jan 2, 2020)

germline

clinical testing

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

SCV002676389

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Oct 21, 2015)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Color Diagnostics, LLC DBA Color Health, SCV001346366.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV002676389.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The p.E287V variant (also known as c.860A>T), located in coding exon 4 of the BARD1 gene, results from an A to T substitution at nucleotide position 860. The glutamic acid at codon 287 is replaced by valine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. This amino acid position is not well conserved however, valine is a reference amino acid in several species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of p.E287V remains unclear.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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