ClinVar Genomic variation as it relates to human health
NM_000465.4(BARD1):c.1148T>A (p.Met383Lys)
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.
Uncertain significance(6); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000465.4(BARD1):c.1148T>A (p.Met383Lys)
Variation ID: 185039 Accession: VCV000185039.27
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q35 2: 214780726 (GRCh38) [ NCBI UCSC ] 2: 215645450 (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 Sep 30, 2017 Oct 13, 2024 Oct 8, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000465.4:c.1148T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000456.2:p.Met383Lys missense NM_001282543.2:c.1091T>A NP_001269472.1:p.Met364Lys missense NM_001282545.2:c.215+16335T>A intron variant NM_001282548.2:c.159-28171T>A intron variant NM_001282549.2:c.364+11571T>A intron variant NR_104212.2:n.1113T>A non-coding transcript variant NR_104215.2:n.1056T>A non-coding transcript variant NC_000002.12:g.214780726A>T NC_000002.11:g.215645450A>T NG_012047.3:g.33986T>A LRG_297:g.33986T>A LRG_297t1:c.1148T>A LRG_297p1:p.Met383Lys - Protein change
- M383K, M364K
- Other names
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- Canonical SPDI
- NC_000002.12:214780725:A: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD) 0.00003
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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
Help
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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Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Jan 11, 2024 | RCV000164393.14 | |
Uncertain significance (3) |
criteria provided, multiple submitters, no conflicts
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Oct 8, 2024 | RCV000462462.14 | |
Uncertain significance (1) |
no assertion criteria provided
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- | RCV001354646.2 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 31, 2017 | RCV000507431.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Jul 21, 2022 | RCV001569258.6 |
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
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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 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000600172.2
First in ClinVar: Sep 30, 2017 Last updated: Jan 01, 2022 |
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Likely benign
(Jan 11, 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: SCV000215029.8
First in ClinVar: Mar 24, 2015 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Oct 31, 2021)
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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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Fulgent Genetics, Fulgent Genetics
Accession: SCV002780800.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Uncertain significance
(Jul 21, 2022)
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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: SCV001793298.3
First in ClinVar: Aug 21, 2021 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer (Adedokun et al., 2020; Uyisenga et al., 2020); This variant is associated with the following publications: (PMID: 32959997, 31871109) (less)
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Uncertain significance
(Feb 16, 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: SCV000682671.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces methionine with lysine at codon 383 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces methionine with lysine at codon 383 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 reported for this variant. This variant has been reported in individuals affected with breast cancer (PMID: 32959997, 35402282). This variant has been identified in 2/282650 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
(Jan 22, 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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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000545603.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 383 of the BARD1 protein (p.Met383Lys). … (more)
This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 383 of the BARD1 protein (p.Met383Lys). This variant is present in population databases (rs763596413, gnomAD 0.008%). This missense change has been observed in individual(s) with breast cancer (PMID: 32959997). ClinVar contains an entry for this variant (Variation ID: 185039). 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 tolerated. 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 08, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV005367995.1
First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024 |
Comment:
This missense variant replaces methionine with lysine at codon 383 of the BARD1 protein. This variant has been identified in 2/282650 chromosomes in the general … (more)
This missense variant replaces methionine with lysine at codon 383 of the BARD1 protein. This variant has been identified in 2/282650 chromosomes in the general population by the Genome Aggregation Database (gnomAD). This variant has been reported in individuals affected with breast cancer (PMID: 32959997, 35402282).In silico analysis supports that this missense variant does not alter protein structure/function.Functional studies have not been reported for this variant.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)
Age: 30-39 years
Sex: female
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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Familial ovarian cancer
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549311.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The BARD1 p.Met383Lys variant was not identified in the literature nor was it identified in the Cosmic, MutDB, or Zhejiang University databases. The variant was … (more)
The BARD1 p.Met383Lys variant was not identified in the literature nor was it identified in the Cosmic, MutDB, or Zhejiang University databases. The variant was identified in dbSNP (ID: rs763596413) as "With Uncertain significance allele" and ClinVar (classified as uncertain significance by Ambry Genetics, Invitae, Color Genomics, and one other clinical laboratory). The variant was identified in control databases in 2 of 276950 chromosomes at a frequency of 0.000007 (Genome Aggregation Database Feb 27, 2017), specifically in the African population in 2 of 24030 chromosomes (freq: 0.000083), while the variant was not observed in the Other, Latino, European, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Met383 residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. 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 |
Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario. | Lerner-Ellis J | Journal of cancer research and clinical oncology | 2021 | PMID: 32885271 |
Screening of germline mutations in young Rwandan patients with breast cancers. | Uyisenga JP | Molecular genetics & genomic medicine | 2020 | PMID: 32959997 |
Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon. | Adedokun B | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2020 | PMID: 31871109 |
Text-mined citations for rs763596413 ...
HelpRecord last updated Oct 13, 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.