NM_000465.4(BARD1):c.457_460dup (p.Val154fs) AND Familial cancer of breast

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 18, 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:: RCV000688045.9

Allele description [Variation Report for NM_000465.4(BARD1):c.457_460dup (p.Val154fs)]

NM_000465.4(BARD1):c.457_460dup (p.Val154fs)

Gene:

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

Variant type:

Duplication

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_000465.4(BARD1):c.457_460dup (p.Val154fs)

HGVS:

NC_000002.12:g.214781417_214781420dup
NG_012047.3:g.33295_33298dup
NM_000465.4:c.457_460dupMANE SELECT
NM_001282543.2:c.400_403dup
NM_001282545.2:c.215+15644_215+15647dup
NM_001282548.2:c.158+27995_158+27998dup
NM_001282549.2:c.364+10880_364+10883dup
NP_000456.2:p.Val154fs
NP_001269472.1:p.Val135fs
LRG_297t1:c.457_460dup
LRG_297:g.33295_33298dup
LRG_297p1:p.Val154fs
NC_000002.11:g.215646137_215646138insCTTT
NC_000002.11:g.215646141_215646144dup
NG_012047.2:g.33288_33291dup
NM_000465.2:c.457_460dupAAAG
NM_000465.3:c.457_460dupAAAG
NR_104212.2:n.422_425dup
NR_104215.2:n.365_368dup

Protein change:

V135fs

Links:

dbSNP: rs772486760

NCBI 1000 Genomes Browser:

rs772486760

Molecular consequence:

NM_000465.4:c.457_460dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.400_403dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.215+15644_215+15647dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+27995_158+27998dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+10880_364+10883dup - intron variant - [Sequence Ontology: SO:0001627]
NR_104212.2:n.422_425dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.365_368dup - 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
SCV000815642	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 27433846, 20077502, 21344236, 28492532
SCV004044322	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 18, 2023)	unknown	clinical testing	Citation Link,
SCV004217330	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 29, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815642

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2022)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004044322

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(May 18, 2023)

unknown

clinical testing

Citation Link,

SCV004217330

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 29, 2022)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

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

Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

Pritchard CC, Mateo J, Walsh MF, De Sarkar N, Abida W, Beltran H, Garofalo A, Gulati R, Carreira S, Eeles R, Elemento O, Rubin MA, Robinson D, Lonigro R, Hussain M, Chinnaiyan A, Vinson J, Filipenko J, Garraway L, Taplin ME, AlDubayan S, Han GC, et al.

N Engl J Med. 2016 Aug 4;375(5):443-53. doi: 10.1056/NEJMoa1603144. Epub 2016 Jul 6.

PubMed [citation]

PMID:: 27433846
PMCID:: PMC4986616

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000815642.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 230344). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). This variant is present in population databases (rs772486760, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Val154Glufs*8) 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., SCV004044322.2

#	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

From Baylor Genetics, SCV004217330.1

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

#	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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