ClinVar Genomic variation as it relates to human health
NM_000465.4(BARD1):c.1108C>T (p.Arg370Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000465.4(BARD1):c.1108C>T (p.Arg370Cys)
Variation ID: 141239 Accession: VCV000141239.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 214780766 (GRCh38) [ NCBI UCSC ] 2: 215645490 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Feb 19, 2018 May 1, 2024 Jan 2, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000465.4:c.1108C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000456.2:p.Arg370Cys missense NM_001282543.2:c.1051C>T NP_001269472.1:p.Arg351Cys missense NM_001282545.2:c.215+16295C>T intron variant NM_001282548.2:c.159-28211C>T intron variant NM_001282549.2:c.364+11531C>T intron variant NR_104212.2:n.1073C>T non-coding transcript variant NR_104215.2:n.1016C>T non-coding transcript variant NC_000002.12:g.214780766G>A NC_000002.11:g.215645490G>A NG_012047.3:g.33946C>T LRG_297:g.33946C>T LRG_297t1:c.1108C>T LRG_297p1:p.Arg370Cys - Protein change
- R370C, R351C
- Other names
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- Canonical SPDI
- NC_000002.12:214780765:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00002
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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BARD1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3943 | 3997 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Mar 31, 2023 | RCV000129660.14 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Jan 2, 2024 | RCV000232099.13 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jun 12, 2023 | RCV000985344.8 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(May 08, 2017)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000785149.2
First in ClinVar: Jul 14, 2018 Last updated: Jul 14, 2018 |
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Uncertain significance
(Apr 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001133433.2
First in ClinVar: Jan 05, 2020 Last updated: Jan 01, 2022 |
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Uncertain significance
(Jun 12, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001771575.4
First in ClinVar: Aug 07, 2021 Last updated: Jun 17, 2023 |
Comment:
In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Abdel-Razeq et al., 2022); This … (more)
In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with breast cancer (Abdel-Razeq et al., 2022); This variant is associated with the following publications: (PMID: 35402282) (less)
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Uncertain significance
(Feb 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004019279.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
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.
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Uncertain significance
(Aug 30, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004217183.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Jan 02, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000284894.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 370 of the BARD1 protein … (more)
This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 370 of the BARD1 protein (p.Arg370Cys). This variant is present in population databases (rs587781596, gnomAD 0.02%). 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: 141239). 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 cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. (less)
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Uncertain significance
(Oct 26, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000184458.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.R370C variant (also known as c.1108C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide … (more)
The p.R370C variant (also known as c.1108C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide position 1108. The arginine at codon 370 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was detected in 1/1197 patients with breast cancer who underwent genetic testing (Abdel-Razeq H et al. Front Oncol, 2022 Mar;12:673094). This amino acid position is poorly conserved in available vertebrate 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 this alteration remains unclear. (less)
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Uncertain significance
(Mar 31, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000682669.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces arginine with cysteine at codon 370 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces arginine with cysteine at codon 370 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been performed for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 33471991, 35402282). In a large breast cancer case-control study, this variant has been observed in 5/60461 cases and 8/53453 controls (OR=0.553, 95%CI 0.181 to 1.689, p-value=0.406; PMID: 33471991). This variant has been identified in 10/251282 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Rates of Variants of Uncertain Significance Among Patients With Breast Cancer Undergoing Genetic Testing: Regional Perspectives. | Abdel-Razeq H | Frontiers in oncology | 2022 | PMID: 35402282 |
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Text-mined citations for rs587781596 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.