VCV000182030.31 - ClinVar

NM_000465.4(BARD1):c.90T>A (p.Gly30=)

Germline

Classification

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.

(11)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000465.4(BARD1):c.90T>A (p.Gly30=)

Variation ID: 182030 Accession: VCV000182030.31

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q35 2: 214809480 (GRCh38) [ NCBI UCSC ] 2: 215674204 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	Jun 1, 2016	Oct 8, 2024	Jan 28, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_000465.4:c.90T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000456.2:p.Gly30=	synonymous
NM_001282543.2:c.90T>A	NP_001269472.1:p.Gly30=	synonymous
NM_001282545.2:c.90T>A	NP_001269474.1:p.Gly30=	synonymous
NM_001282548.2:c.90T>A	NP_001269477.1:p.Gly30=	synonymous
NM_001282549.2:c.90T>A	NP_001269478.1:p.Gly30=	synonymous
NR_104212.2:n.204T>A		non-coding transcript variant
NR_104215.2:n.204T>A		non-coding transcript variant
NR_104216.2:n.204T>A		non-coding transcript variant
NC_000002.12:g.214809480A>T
NC_000002.11:g.215674204A>T
NG_012047.3:g.5232T>A
LRG_297:g.5232T>A
LRG_297t1:c.90T>A	LRG_297p1:p.Gly30=

... more HGVS ... less HGVS

Protein change

Other names

p.G30G:GGT>GGA
NP_000456.2:p.Gly30=

Canonical SPDI

NC_000002.12:214809479:A:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00060 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00015

Exome Aggregation Consortium (ExAC) 0.00016

1000 Genomes Project 30x 0.00047

1000 Genomes Project 0.00060

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00081

Trans-Omics for Precision Medicine (TOPMed) 0.00081

The Genome Aggregation Database (gnomAD) 0.00088

Links

ClinGen: CA298433 dbSNP: rs150354152 VarSome

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
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help 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.
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 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 Help 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.
Hereditary cancer-predisposing syndrome	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Apr 2, 2021	RCV000159799.11
not specified	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jun 21, 2019	RCV000212109.9
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Feb 9, 2023	RCV000589905.7
Familial cancer of breast	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 28, 2024	RCV001086278.13
Hereditary breast ovarian cancer syndrome	Likely benign (1)	criteria provided, single submitter	Apr 19, 2022	RCV002225461.2
BARD1-related disorder	Likely benign (1)	no assertion criteria provided	Apr 29, 2019	RCV003952795.2

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.
Benign (Aug 07, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000209823.10 First in ClinVar: Feb 24, 2015 Last updated: Jun 01, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (May 02, 2016)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000696793.1 First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018	Publications: PubMed (1) PubMed: 26787654 Comment: Variant summary: The c.90T>A (p.Gly30=) in BARD1 gene is a synonymous change that involves a non-conserved nucleotide. 3/5 programs in Alamut predict that this variant … (more) Variant summary: The c.90T>A (p.Gly30=) in BARD1 gene is a synonymous change that involves a non-conserved nucleotide. 3/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00016 (16/98040 chrs tested), exclusively in individuals of African origin (0.0025; 16/6376 control chrs). This frequency exceeds the maximal expected frequency of a pathogenic allele (0.000125) in this gene. The variant of interest was cited as Benign/Likely Benign by multiple reputable clinical laboratories. Taking together, the variant was classified as Benign. (less)
Benign (Feb 09, 2023)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000888813.4 First in ClinVar: Mar 17, 2018 Last updated: Jan 06, 2024	Publications: PubMed (1) PubMed: 26787654
Likely benign (Oct 07, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000214383.7 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)
Likely benign (Jun 21, 2019)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001160621.1 First in ClinVar: Feb 10, 2020 Last updated: Feb 10, 2020
Likely benign (Jan 13, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Familial cancer of breast Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427226.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more) This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Likely benign (Apr 19, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: yes Allele origin: germline	National Health Laboratory Service, Universitas Academic Hospital and University of the Free State Accession: SCV002505145.1 First in ClinVar: Apr 29, 2022 Last updated: Apr 29, 2022	Number of individuals with the variant: 3 Geographic origin: South Africa
Likely benign (Apr 02, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002529661.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Benign (Apr 28, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000682823.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Benign (Jan 28, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Familial cancer of breast Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000261390.11 First in ClinVar: Jan 31, 2016 Last updated: Feb 20, 2024
Likely benign (Apr 29, 2019)	no assertion criteria provided Method: clinical testing	BARD1-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004772622.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

Variant summary: The c.90T>A (p.Gly30=) in BARD1 gene is a synonymous change that involves a non-conserved nucleotide. 3/5 programs in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.00016 (16/98040 chrs tested), exclusively in individuals of African origin (0.0025; 16/6376 control chrs). This frequency exceeds the maximal expected frequency of a pathogenic allele (0.000125) in this gene. The variant of interest was cited as Benign/Likely Benign by multiple reputable clinical laboratories. Taking together, the variant was classified as Benign.

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 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.

Comment:

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Multigene testing of moderate-risk genes: be mindful of the missense.	Young EL	Journal of medical genetics	2016	PMID: 26787654

Text-mined citations for rs150354152 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_000465.4(BARD1):c.90T>A (p.Gly30=)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs150354152 ...