NM_000465.4(BARD1):c.1002del (p.Arg335fs) AND Familial cancer of breast

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 22, 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:: RCV001058680.9

Allele description [Variation Report for NM_000465.4(BARD1):c.1002del (p.Arg335fs)]

NM_000465.4(BARD1):c.1002del (p.Arg335fs)

Gene:

BARD1:BRCA1 associated RING domain 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_000465.4(BARD1):c.1002del (p.Arg335fs)

HGVS:

NC_000002.12:g.214780872del
NG_012047.3:g.33840del
NM_000465.4:c.1002delMANE SELECT
NM_001282543.2:c.945del
NM_001282545.2:c.215+16189del
NM_001282548.2:c.159-28317del
NM_001282549.2:c.364+11425del
NP_000456.2:p.Arg335fs
NP_001269472.1:p.Arg316fs
LRG_297t1:c.1002del
LRG_297:g.33840del
LRG_297p1:p.Arg335fs
NC_000002.11:g.215645596del
NG_012047.2:g.33833del
NM_000465.3:c.1002del
NR_104212.2:n.967del
NR_104215.2:n.910del

Protein change:

R316fs

Links:

dbSNP: rs1694972839

NCBI 1000 Genomes Browser:

rs1694972839

Molecular consequence:

NM_000465.4:c.1002del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.945del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.215+16189del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.159-28317del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+11425del - intron variant - [Sequence Ontology: SO:0001627]
NR_104212.2:n.967del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.910del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001223267	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 12, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20077502, 21344236, 28492532
SCV004042980	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 22, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001223267

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 12, 2022)

germline

clinical testing

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

SCV004042980

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(May 22, 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	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001223267.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 853796). 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.Arg335Aspfs*7) 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 Myriad Genetics, Inc., SCV004042980.2

#	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 frameshift 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 29, 2024

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