NM_000465.4(BARD1):c.2268G>A (p.Trp756Ter) AND Familial cancer of breast

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 31, 2023
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:: RCV003500508.1

Allele description [Variation Report for NM_000465.4(BARD1):c.2268G>A (p.Trp756Ter)]

NM_000465.4(BARD1):c.2268G>A (p.Trp756Ter)

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.2268G>A (p.Trp756Ter)

HGVS:

NC_000002.12:g.214728742C>T
NG_012047.3:g.85970G>A
NM_000465.4:c.2268G>AMANE SELECT
NM_001282543.2:c.2211G>A
NM_001282545.2:c.915G>A
NM_001282548.2:c.858G>A
NM_001282549.2:c.729G>A
NP_000456.2:p.Trp756Ter
NP_001269472.1:p.Trp737Ter
NP_001269474.1:p.Trp305Ter
NP_001269477.1:p.Trp286Ter
NP_001269478.1:p.Trp243Ter
LRG_297t1:c.2268G>A
LRG_297:g.85970G>A
LRG_297p1:p.Trp756Ter
NC_000002.11:g.215593466C>T
NG_012047.2:g.85963G>A
NM_000465.2:c.2268G>A
NR_104212.2:n.2233G>A
NR_104215.2:n.2176G>A
NR_104216.2:n.1432G>A
p.W756*

Protein change:

W243*

Links:

dbSNP: rs786202118

NCBI 1000 Genomes Browser:

rs786202118

Molecular consequence:

NR_104212.2:n.2233G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.2176G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1432G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000465.4:c.2268G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282543.2:c.2211G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282545.2:c.915G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282548.2:c.858G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282549.2:c.729G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004293074	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Aug 31, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17848578, 30925164, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004293074

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Aug 31, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Structural requirements for the BARD1 tumor suppressor in chromosomal stability and homology-directed DNA repair.

Laufer M, Nandula SV, Modi AP, Wang S, Jasin M, Murty VV, Ludwig T, Baer R.

J Biol Chem. 2007 Nov 23;282(47):34325-33. Epub 2007 Sep 11.

PubMed [citation]

PMID:: 17848578

Functional analysis of BARD1 missense variants in homology-directed repair and damage sensitivity.

Adamovich AI, Banerjee T, Wingo M, Duncan K, Ning J, Martins Rodrigues F, Huang KL, Lee C, Chen F, Ding L, Parvin JD.

PLoS Genet. 2019 Mar;15(3):e1008049. doi: 10.1371/journal.pgen.1008049.

PubMed [citation]

PMID:: 30925164
PMCID:: PMC6457558

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV004293074.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Trp756*) in the BARD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 22 amino acid(s) of the BARD1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 185366). This variant disrupts the C-terminal BRCT domain of BARD1 protein, which is required for chromosome stability and homology-directed repair (PMID: 17848578). A different variant (p.Val767fs) that lies downstream of this variant has been reported to affect BARD1 protein function (PMID: 30925164), this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been 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: May 7, 2024

ClinVar

Relating variation to medicine