NM_000465.4(BARD1):c.2284T>C (p.Trp762Arg) AND Familial cancer of breast

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Mar 25, 2024
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:: RCV000231169.13

Allele description [Variation Report for NM_000465.4(BARD1):c.2284T>C (p.Trp762Arg)]

NM_000465.4(BARD1):c.2284T>C (p.Trp762Arg)

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.2284T>C (p.Trp762Arg)

HGVS:

NC_000002.12:g.214728726A>G
NG_012047.3:g.85986T>C
NM_000465.4:c.2284T>CMANE SELECT
NM_001282543.2:c.2227T>C
NM_001282545.2:c.931T>C
NM_001282548.2:c.874T>C
NM_001282549.2:c.745T>C
NP_000456.2:p.Trp762Arg
NP_001269472.1:p.Trp743Arg
NP_001269474.1:p.Trp311Arg
NP_001269477.1:p.Trp292Arg
NP_001269478.1:p.Trp249Arg
LRG_297t1:c.2284T>C
LRG_297:g.85986T>C
LRG_297p1:p.Trp762Arg
NC_000002.11:g.215593450A>G
NG_012047.2:g.85979T>C
NM_000465.2:c.2284T>C
NM_000465.3:c.2284T>C
NR_104212.2:n.2249T>C
NR_104215.2:n.2192T>C
NR_104216.2:n.1448T>C

Protein change:

W249R

Links:

dbSNP: rs878854008

NCBI 1000 Genomes Browser:

rs878854008

Molecular consequence:

NM_000465.4:c.2284T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.2227T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.931T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.874T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.745T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.2249T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.2192T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1448T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
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
SCV000284951	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 29, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000786158	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Mar 12, 2018)	unknown	clinical testing	Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004019273	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Feb 24, 2023)	unknown	clinical testing	Citation Link,
SCV005053314	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 25, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000284951.8

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

Description

This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 762 of the BARD1 protein (p.Trp762Arg). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 237832). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Counsyl, SCV000786158.2

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

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

From Myriad Genetics, Inc., SCV004019273.1

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

Description

This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

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

From Baylor Genetics, SCV005053314.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine