NM_000465.4(BARD1):c.334C>T (p.Arg112Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 3, 2022
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:: RCV000164507.9

Allele description [Variation Report for NM_000465.4(BARD1):c.334C>T (p.Arg112Ter)]

NM_000465.4(BARD1):c.334C>T (p.Arg112Ter)

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.334C>T (p.Arg112Ter)

HGVS:

NC_000002.12:g.214792327G>A
NG_012047.3:g.22385C>T
NM_000465.4:c.334C>TMANE SELECT
NM_001282543.2:c.277C>T
NM_001282545.2:c.215+4734C>T
NM_001282548.2:c.158+17085C>T
NM_001282549.2:c.334C>T
NP_000456.2:p.Arg112Ter
NP_001269472.1:p.Arg93Ter
NP_001269478.1:p.Arg112Ter
LRG_297t1:c.334C>T
LRG_297:g.22385C>T
LRG_297p1:p.Arg112Ter
NC_000002.11:g.215657051G>A
NG_012047.2:g.22378C>T
NM_000465.2:c.334C>T
NM_000465.3:c.334C>T
NR_104216.2:n.448C>T
p.R112*

Protein change:

R112*

Links:

dbSNP: rs758972589

NCBI 1000 Genomes Browser:

rs758972589

Molecular consequence:

NM_001282545.2:c.215+4734C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+17085C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_104216.2:n.448C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000465.4:c.334C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282543.2:c.277C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282549.2:c.334C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000215158	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Aug 3, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23334666, 27083178, 28724667 Citation Link,
SCV001357309	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 15, 2020)	germline	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

SCV000215158

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Aug 3, 2022)

germline

clinical testing

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

Citation Link,

SCV001357309

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 15, 2020)

germline

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

Citations

PubMed

The genetic landscape of high-risk neuroblastoma.

Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, Carter SL, Cibulskis K, Hanna M, Kiezun A, Kim J, Lawrence MS, Lichenstein L, McKenna A, Pedamallu CS, Ramos AH, Shefler E, Sivachenko A, Sougnez C, Stewart C, Ally A, Birol I, et al.

Nat Genet. 2013 Mar;45(3):279-84. doi: 10.1038/ng.2529. Epub 2013 Jan 20.

PubMed [citation]

PMID:: 23334666
PMCID:: PMC3682833

Frequency of germline DNA genetic findings in an unselected prospective cohort of triple-negative breast cancer patients participating in a platinum-based neoadjuvant chemotherapy trial.

González-Rivera M, Lobo M, López-Tarruella S, Jerez Y, Del Monte-Millán M, Massarrah T, Ramos-Medina R, Ocaña I, Picornell A, Santillán Garzón S, Pérez-Carbornero L, García-Saenz JA, Gómez H, Moreno F, Márquez-Rodas I, Fuentes H, Martin M.

Breast Cancer Res Treat. 2016 Apr;156(3):507-515. doi: 10.1007/s10549-016-3792-1. Epub 2016 Apr 15. Erratum in: Breast Cancer Res Treat. 2017 Sep;165(2):471. doi: 10.1007/s10549-017-4396-0.

PubMed [citation]

PMID:: 27083178

See all PubMed Citations (4)

Details of each submission

From Ambry Genetics, SCV000215158.7

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

Description

The p.R112* pathogenic mutation (also known as c.334C>T), located in coding exon 3 of the BARD1 gene, results from a C to T substitution at nucleotide position 334. This changes the amino acid from an arginine to a stop codon within coding exon 3. This alteration was detected in a cohort of 8085 consecutive unselected Chinese breast cancer patients who underwent multi-gene panel testing (Sun L et al. Clin. Cancer Res. 2017 Oct;23(20):6113-6119), and has been reported in 1 of 124 patients with stage II-III triple negative breast cancer (González-Rivera M et al. Breast Cancer Res. Treat. 2016 Apr;156:507-515). This alteration has also been reported as a germline mutation in a cohort of patients with neuroblastoma tumors (Pugh TJ et al. Nat. Genet. 2013 Mar; 45(3):279-84. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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 Color Diagnostics, LLC DBA Color Health, SCV001357309.2

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

Description

This variant changes 1 nucleotide in exon 3 of the BARD1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been identified in 2/251010 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BARD1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	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

Last Updated: Sep 29, 2024

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