NM_000465.4(BARD1):c.102G>A (p.Trp34Ter) AND Familial cancer of breast

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 19, 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:: RCV000699165.10

Allele description [Variation Report for NM_000465.4(BARD1):c.102G>A (p.Trp34Ter)]

NM_000465.4(BARD1):c.102G>A (p.Trp34Ter)

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.102G>A (p.Trp34Ter)

HGVS:

NC_000002.12:g.214809468C>T
NG_012047.3:g.5244G>A
NM_000465.4:c.102G>AMANE SELECT
NM_001282543.2:c.102G>A
NM_001282545.2:c.102G>A
NM_001282548.2:c.102G>A
NM_001282549.2:c.102G>A
NP_000456.2:p.Trp34Ter
NP_001269472.1:p.Trp34Ter
NP_001269474.1:p.Trp34Ter
NP_001269477.1:p.Trp34Ter
NP_001269478.1:p.Trp34Ter
LRG_297t1:c.102G>A
LRG_297:g.5244G>A
LRG_297p1:p.Trp34Ter
NC_000002.11:g.215674192C>T
NG_012047.2:g.5237G>A
NM_000465.2:c.102G>A
NM_000465.3:c.102G>A
NR_104212.2:n.216G>A
NR_104215.2:n.216G>A
NR_104216.2:n.216G>A

Protein change:

W34*

Links:

dbSNP: rs879254280

NCBI 1000 Genomes Browser:

rs879254280

Molecular consequence:

NR_104212.2:n.216G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.216G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.216G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000465.4:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282543.2:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282545.2:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282548.2:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001282549.2:c.102G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Familial cancer of breast
Synonyms:: Breast cancer, familial; Hereditary breast cancer
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000827863	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20077502, 21344236, 28492532
SCV002589051	BRCAlab, Lund University	no assertion criteria provided	Pathogenic (Aug 26, 2022)	germline	clinical testing
SCV004043612	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 17, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000827863

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002589051

BRCAlab, Lund University

no assertion criteria provided

Pathogenic
(Aug 26, 2022)

germline

clinical testing

SCV004043612

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(May 17, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

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

Cancer predisposing missense and protein truncating BARD1 mutations in non-BRCA1 or BRCA2 breast cancer families.

De Brakeleer S, De Grève J, Loris R, Janin N, Lissens W, Sermijn E, Teugels E.

Hum Mutat. 2010 Mar;31(3):E1175-85. doi: 10.1002/humu.21200.

PubMed [citation]

PMID:: 20077502

Cancer predisposing BARD1 mutations in breast-ovarian cancer families.

Ratajska M, Antoszewska E, Piskorz A, Brozek I, Borg Å, Kusmierek H, Biernat W, Limon J.

Breast Cancer Res Treat. 2012 Jan;131(1):89-97. doi: 10.1007/s10549-011-1403-8. Epub 2011 Feb 23.

PubMed [citation]

PMID:: 21344236

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000827863.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 246476). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with BARD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp34*) in the BARD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236).

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

From BRCAlab, Lund University, SCV002589051.1

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

#	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	1	not provided

From Myriad Genetics, Inc., SCV004043612.2

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

Description

This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

#	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: Sep 8, 2024

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