NM_000465.4(BARD1):c.448C>T (p.Arg150Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 2, 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:: RCV000213814.10

Allele description [Variation Report for NM_000465.4(BARD1):c.448C>T (p.Arg150Ter)]

NM_000465.4(BARD1):c.448C>T (p.Arg150Ter)

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.448C>T (p.Arg150Ter)

Other names:

p.R150*:CGA>TGA

HGVS:

NC_000002.12:g.214781426G>A
NG_012047.3:g.33286C>T
NM_000465.4:c.448C>TMANE SELECT
NM_001282543.2:c.391C>T
NM_001282545.2:c.215+15635C>T
NM_001282548.2:c.158+27986C>T
NM_001282549.2:c.364+10871C>T
NP_000456.2:p.Arg150Ter
NP_001269472.1:p.Arg131Ter
LRG_297t1:c.448C>T
LRG_297:g.33286C>T
LRG_297p1:p.Arg150Ter
NC_000002.11:g.215646150G>A
NG_012047.2:g.33279C>T
NM_000465.2:c.448C>T
NM_000465.3:c.448C>T
NR_104212.2:n.413C>T
NR_104215.2:n.356C>T

Protein change:

R131*

Links:

dbSNP: rs730881411

NCBI 1000 Genomes Browser:

rs730881411

Molecular consequence:

NM_001282545.2:c.215+15635C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+27986C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+10871C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_104212.2:n.413C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.356C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000465.4:c.448C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001282543.2:c.391C>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
SCV000273117	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 2, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26681312, 28709830 Citation Link,
SCV000911007	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 6, 2021)	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

SCV000273117

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 2, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000911007

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 6, 2021)

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

Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.

Susswein LR, Marshall ML, Nusbaum R, Vogel Postula KJ, Weissman SM, Yackowski L, Vaccari EM, Bissonnette J, Booker JK, Cremona ML, Gibellini F, Murphy PD, Pineda-Alvarez DE, Pollevick GD, Xu Z, Richard G, Bale S, Klein RT, Hruska KS, Chung WK.

Genet Med. 2016 Aug;18(8):823-32. doi: 10.1038/gim.2015.166. Epub 2015 Dec 17. Erratum in: Genet Med. 2016 May;18(5):531-2. doi: 10.1038/gim.2016.21.

PubMed [citation]

PMID:: 26681312
PMCID:: PMC4985612

Pathologic findings in breast, fallopian tube, and ovary specimens in non-BRCA hereditary breast and/or ovarian cancer syndromes: a study of 18 patients with deleterious germline mutations in RAD51C, BARD1, BRIP1, PALB2, MUTYH, or CHEK2.

Schoolmeester JK, Moyer AM, Goodenberger ML, Keeney GL, Carter JM, Bakkum-Gamez JN.

Hum Pathol. 2017 Dec;70:14-26. doi: 10.1016/j.humpath.2017.06.018. Epub 2017 Jul 12.

PubMed [citation]

PMID:: 28709830

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000273117.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R150* pathogenic mutation (also known as c.448C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide position 448. This changes the amino acid from an arginine to a stop codon within coding exon 4. This mutation has previously been reported in the literature in two patients with breast cancer, one of whom also had a family history of breast and ovarian cancer in first and second degree relatives (Susswein LR et al. Genet. Med. 2016 Aug;18:823-32; Schoolmeester JK et al. Hum. Pathol. 2017 Dec;70:14-26). 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, SCV000911007.3

#	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 4 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 reported in individuals affected with breast, ovarian, and pancreatic cancer (PMID: 26681312, 26720728, 28709830, 29922827, 31036035, 32566746). This variant has been identified in 2/250728 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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