NM_000465.4(BARD1):c.1922G>A (p.Arg641Gln) AND Familial cancer of breast

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 13, 2023
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:: RCV000232354.15

Allele description [Variation Report for NM_000465.4(BARD1):c.1922G>A (p.Arg641Gln)]

NM_000465.4(BARD1):c.1922G>A (p.Arg641Gln)

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.1922G>A (p.Arg641Gln)

HGVS:

NC_000002.12:g.214730490C>T
NG_012047.3:g.84222G>A
NM_000465.4:c.1922G>AMANE SELECT
NM_001282543.2:c.1865G>A
NM_001282545.2:c.569G>A
NM_001282548.2:c.512G>A
NM_001282549.2:c.383G>A
NP_000456.2:p.Arg641Gln
NP_001269472.1:p.Arg622Gln
NP_001269474.1:p.Arg190Gln
NP_001269477.1:p.Arg171Gln
NP_001269478.1:p.Arg128Gln
LRG_297t1:c.1922G>A
LRG_297:g.84222G>A
LRG_297p1:p.Arg641Gln
NC_000002.11:g.215595214C>T
NG_012047.2:g.84215G>A
NM_000465.2:c.1922G>A
NM_000465.3:c.1922G>A
NR_104212.2:n.1887G>A
NR_104215.2:n.1830G>A
NR_104216.2:n.1086G>A

Protein change:

R128Q

Links:

dbSNP: rs752870879

NCBI 1000 Genomes Browser:

rs752870879

Molecular consequence:

NM_000465.4:c.1922G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.1865G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.569G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.512G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.383G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.1887G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.1830G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.1086G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

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

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Lupinus angustifolius cultivar Tanjil chromosome LG13 genomic scaffold Scaffold_114_12, whole genome shotgun sequence
gi|1102699557|gb|KV861939.1||gnl|WG U01|Scaffold_114_12

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000284934	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 13, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30925164, 28492532
SCV002580182	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000284934

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 13, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002580182

MGZ Medical Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 3, 2023)

germline

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	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000284934.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 641 of the BARD1 protein (p.Arg641Gln). This variant is present in population databases (rs752870879, 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: 231509). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect BARD1 function (PMID: 30925164). 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 MGZ Medical Genetics Center, SCV002580182.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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