NM_000465.4(BARD1):c.225_228del (p.Ser76fs) AND Familial cancer of breast

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002530247.3

Allele description [Variation Report for NM_000465.4(BARD1):c.225_228del (p.Ser76fs)]

NM_000465.4(BARD1):c.225_228del (p.Ser76fs)

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.225_228del (p.Ser76fs)

HGVS:

NC_000002.12:g.214792435_214792438del
NG_012047.3:g.22276_22279del
NM_000465.4:c.225_228delMANE SELECT
NM_001282543.2:c.168_171del
NM_001282545.2:c.215+4625_215+4628del
NM_001282548.2:c.158+16976_158+16979del
NM_001282549.2:c.225_228del
NP_000456.2:p.Ser76fs
NP_001269472.1:p.Ser57fs
NP_001269478.1:p.Ser76fs
LRG_297t1:c.225_228del
LRG_297:g.22276_22279del
LRG_297p1:p.Ser76fs
NC_000002.11:g.215657157_215657160del
NC_000002.11:g.215657159_215657162del
NG_012047.2:g.22269_22272del
NM_000465.2:c.225_228delAAGT
NR_104216.2:n.339_342del

Protein change:

S57fs

Links:

dbSNP: rs1553624830

NCBI 1000 Genomes Browser:

rs1553624830

Molecular consequence:

NM_000465.4:c.225_228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.168_171del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282549.2:c.225_228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.215+4625_215+4628del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+16976_158+16979del - intron variant - [Sequence Ontology: SO:0001627]
NR_104216.2:n.339_342del - 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
SCV003525191	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20077502, 21344236, 28486781, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525191

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2023)

germline

clinical testing

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

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

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 (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003525191.2

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

Description

This sequence change creates a premature translational stop signal (p.Ser76Thrfs*19) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with breast cancer (PMID: 28486781). This variant is also known as c.225delACTT. ClinVar contains an entry for this variant (Variation ID: 481396). For these reasons, this variant has been 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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