NM_000465.4(BARD1):c.740del (p.Ser247fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic/Likely 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:: RCV002258546.4

Allele description [Variation Report for NM_000465.4(BARD1):c.740del (p.Ser247fs)]

NM_000465.4(BARD1):c.740del (p.Ser247fs)

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.740del (p.Ser247fs)

HGVS:

NC_000002.12:g.214781134del
NG_012047.3:g.33578del
NM_000465.4:c.740delMANE SELECT
NM_001282543.2:c.683del
NM_001282545.2:c.215+15927del
NM_001282548.2:c.158+28278del
NM_001282549.2:c.364+11163del
NP_000456.2:p.Ser247fs
NP_001269472.1:p.Ser228fs
LRG_297t1:c.740del
LRG_297:g.33578del
LRG_297p1:p.Ser247fs
NC_000002.11:g.215645858del
NM_000465.2:c.740delC
NR_104212.2:n.705del
NR_104215.2:n.648del

Protein change:

S228fs

Links:

dbSNP: rs2106110712

NCBI 1000 Genomes Browser:

rs2106110712

Molecular consequence:

NM_000465.4:c.740del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.683del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.215+15927del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+28278del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+11163del - intron variant - [Sequence Ontology: SO:0001627]
NR_104212.2:n.705del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.648del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

Recent activity

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Homo sapiens tRNA methyltransferase activator subunit 11-2 (TRMT112), transcript...
Homo sapiens tRNA methyltransferase activator subunit 11-2 (TRMT112), transcript variant 1, mRNA
gi|1720121869|ref|NM_016404.3|

Nucleotide
Homologene neighbors for GEO Profiles (Select 131960694) (0)
GEO Profiles
Profile neighbors for GEO Profiles (Select 131960695) (199)
GEO Profiles
Chromosome neighbors for GEO Profiles (Select 131973555) (20)
GEO Profiles
Helobdella robusta unplaced genomic scaffold HELROscaffold_1, whole genome shotg...
Helobdella robusta unplaced genomic scaffold HELROscaffold_1, whole genome shotgun sequence
gi|431834951|gnl|WGS:AMQM01|HELROsc d_1|gb|KB095811.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002529651	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Likely pathogenic (Mar 2, 2022)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002673108	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 22, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002529651

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Likely pathogenic
(Mar 2, 2022)

germline

curation

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

Citation Link,

SCV002673108

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 22, 2021)

germline

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, curation

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

Details of each submission

From Sema4, Sema4, SCV002529651.1

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

#	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 Ambry Genetics, SCV002673108.2

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

Description

The c.740delC pathogenic mutation, located in coding exon 4 of the BARD1 gene, results from a deletion of one nucleotide at nucleotide position 740, causing a translational frameshift with a predicted alternate stop codon (p.S247Lfs*8). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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

Last Updated: May 7, 2024

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