NM_000465.4(BARD1):c.159-1G>T AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic/Likely pathogenic (4 submissions)
Last evaluated:: Jun 14, 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:: RCV000235953.12

Allele description

NM_000465.4(BARD1):c.159-1G>T

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.159-1G>T

HGVS:

NC_000002.12:g.214797118C>A
NG_012047.3:g.17594G>T
NM_000465.4:c.159-1G>TMANE SELECT
NM_001282543.2:c.159-4673G>T
NM_001282545.2:c.159-1G>T
NM_001282548.2:c.158+12294G>T
NM_001282549.2:c.159-1G>T
LRG_297t1:c.159-1G>T
LRG_297:g.17594G>T
NC_000002.11:g.215661842C>A
NM_000465.2:c.159-1G>T
NM_000465.3:c.159-1G>T

Links:

dbSNP: rs879254139

NCBI 1000 Genomes Browser:

rs879254139

Molecular consequence:

NM_001282543.2:c.159-4673G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+12294G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000465.4:c.159-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282545.2:c.159-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001282549.2:c.159-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000293620	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Nov 22, 2022)	germline	clinical testing	Citation Link,
SCV002822789	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Oct 1, 2022)	germline	clinical testing	Citation Link,
SCV004026029	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 4, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004221609	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jun 14, 2023)	unknown	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31843900, 31036035, 33809641, 33471991, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Characterization of splice-altering mutations in inherited predisposition to cancer.

Casadei S, Gulsuner S, Shirts BH, Mandell JB, Kortbawi HM, Norquist BS, Swisher EM, Lee MK, Goldberg Y, O'Connor R, Tan Z, Pritchard CC, King MC, Walsh T.

Proc Natl Acad Sci U S A. 2019 Dec 26;116(52):26798-26807. doi: 10.1073/pnas.1915608116. Epub 2019 Dec 16.

PubMed [citation]

PMID:: 31843900
PMCID:: PMC6936554

See all PubMed Citations (6)

Details of each submission

From GeneDx, SCV000293620.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Canonical splice site variant expected to result in aberrant splicing; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies demonstrate a damaging effect: abnormal splicing (Casadei et al., 2019); This variant is associated with the following publications: (PMID: 31843900, 31036035, 33804961, 33809641)

#	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		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV002822789.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

BARD1: PVS1, PM2

#	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		1	not provided	not provided	not provided

From Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden, SCV004026029.1

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

Description

PVS1

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221609.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The BARD1 c.159-1G>T variant disrupts a canonical splice-acceptor site and interferes with normal BARD1 mRNA splicing. This variant has been reported in the published literature in affected individuals with breast cancer (PMIDs: 31036035 (2019) and 33471991 (2021)), ovarian and prostate cancer (PMID: 31843900 (2019)), b-cell neoplasms (PMID: 33809641 (2021)), as well as in a healthy individual (PMID: 33471991 (2021)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 7, 2024

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