ClinVar Genomic variation as it relates to human health
NM_000465.4(BARD1):c.1594G>A (p.Asp532Asn)
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.1594G>A (p.Asp532Asn)
Variation ID: 185716 Accession: VCV000185716.22
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 214752530 (GRCh38) [ NCBI UCSC ] 2: 215617254 (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 Dec 19, 2017 Aug 11, 2024 Jun 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000465.4:c.1594G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000456.2:p.Asp532Asn missense NM_001282543.2:c.1537G>A NP_001269472.1:p.Asp513Asn missense NM_001282545.2:c.241G>A NP_001269474.1:p.Asp81Asn missense NM_001282548.2:c.184G>A NP_001269477.1:p.Asp62Asn missense NM_001282549.2:c.365-22022G>A intron variant NR_104212.2:n.1559G>A non-coding transcript variant NR_104215.2:n.1502G>A non-coding transcript variant NR_104216.2:n.758G>A non-coding transcript variant NC_000002.12:g.214752530C>T NC_000002.11:g.215617254C>T NG_012047.3:g.62182G>A LRG_297:g.62182G>A LRG_297t1:c.1594G>A LRG_297p1:p.Asp532Asn - Protein change
- D532N, D62N, D513N, D81N
- Other names
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- Canonical SPDI
- NC_000002.12:214752529:C:T
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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.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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 |
4007 | 4063 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
Help
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 (3) |
criteria provided, multiple submitters, no conflicts
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Jun 17, 2024 | RCV000165192.14 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Mar 5, 2024 | RCV000459538.14 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jan 31, 2024 | RCV000486325.4 |
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
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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
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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
(Dec 10, 2019)
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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: SCV000688137.4
First in ClinVar: Feb 19, 2018 Last updated: Jan 12, 2022 |
Comment:
This missense variant replaces aspartic acid with asparagine at codon 532 of the BARD1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces aspartic acid with asparagine at codon 532 of the BARD1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251288 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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Uncertain significance
(Jun 24, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002527029.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The BARD1 c.1594G>A (p.D532N) variant has not been reported in the literature to our knowledge. This variant was observed in 2/18394 chromosomes in the East … (more)
The BARD1 c.1594G>A (p.D532N) variant has not been reported in the literature to our knowledge. This variant was observed in 2/18394 chromosomes in the East Asian population, according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID 185716). In silico tools suggest the impact of the variant on protein function is inconclusive, though these predictions have not been confirmed by functional studies. The overall evidence is insufficient to meet ACMG/AMP criteria for classifying it as benign or pathogenic. In summary, the clinical significance of this variant is currently uncertain. (less)
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Uncertain significance
(Jul 02, 2018)
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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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Mendelics
Accession: SCV000837960.2
First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022 |
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Uncertain significance
(Nov 09, 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:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000545637.10
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 532 of the BARD1 protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 532 of the BARD1 protein (p.Asp532Asn). This variant is present in population databases (rs757281184, gnomAD 0.01%). 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: 185716). 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. (less)
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Uncertain significance
(Mar 05, 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:
unknown
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Baylor Genetics
Accession: SCV005054577.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Uncertain significance
(Jan 31, 2024)
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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: SCV000569986.6
First in ClinVar: Apr 29, 2017 Last updated: Jul 23, 2024 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18480049) (less)
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Uncertain significance
(Jun 17, 2024)
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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: SCV000215904.8
First in ClinVar: Mar 24, 2015 Last updated: Aug 11, 2024 |
Comment:
The p.D532N variant (also known as c.1594G>A), located in coding exon 7 of the BARD1 gene, results from a G to A substitution at nucleotide … (more)
The p.D532N variant (also known as c.1594G>A), located in coding exon 7 of the BARD1 gene, results from a G to A substitution at nucleotide position 1594. The aspartic acid at codon 532 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs757281184 ...
HelpRecord last updated Sep 29, 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.