NM_000465.4(BARD1):c.2242G>T (p.Glu748Ter) AND Malignant tumor of breast

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 10, 2022
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:: RCV001844259.2

Allele description [Variation Report for NM_000465.4(BARD1):c.2242G>T (p.Glu748Ter)]

NM_000465.4(BARD1):c.2242G>T (p.Glu748Ter)

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.2242G>T (p.Glu748Ter)

HGVS:

NC_000002.12:g.214728768C>A
NG_012047.3:g.85944G>T
NM_000465.4:c.2242G>TMANE SELECT
NM_001282543.2:c.2185G>T
NM_001282545.2:c.889G>T
NM_001282548.2:c.832G>T
NM_001282549.2:c.703G>T
NP_000456.2:p.Glu748Ter
NP_001269472.1:p.Glu729Ter
NP_001269474.1:p.Glu297Ter
NP_001269477.1:p.Glu278Ter
NP_001269478.1:p.Glu235Ter
LRG_297t1:c.2242G>T
LRG_297:g.85944G>T
LRG_297p1:p.Glu748Ter
NC_000002.11:g.215593492C>A
NG_012047.2:g.85937G>T
NM_000465.2:c.2242G>T
NM_000465.3:c.2242G>T
NR_104212.2:n.2207G>T
NR_104215.2:n.2150G>T
NR_104216.2:n.1406G>T

Protein change:

E235*

Links:

dbSNP: rs879253880

NCBI 1000 Genomes Browser:

rs879253880

Molecular consequence:

NR_104212.2:n.2207G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.2150G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1406G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000465.4:c.2242G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282543.2:c.2185G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282545.2:c.889G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282548.2:c.832G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282549.2:c.703G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002103498	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Feb 10, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002103498

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Feb 10, 2022)

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103498.1

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

Description

Variant summary: BARD1 c.2242G>T (p.Glu748X) results in a premature termination codon, predicted to cause a truncation of the encoded protein, which is a commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic/likely pathogenic in ClinVar. The variant is not expected to cause nonsense mediated decay, but is expected to impact translation of the last 29 amino acids, including a portion of the BRCT domain (IPR001357). The variant was absent in 251284 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2242G>T in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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 8, 2024

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