NM_000465.4(BARD1):c.1817_1818del (p.His606fs) AND Familial cancer of breast

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 27, 2024
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:: RCV000635815.13

Allele description [Variation Report for NM_000465.4(BARD1):c.1817_1818del (p.His606fs)]

NM_000465.4(BARD1):c.1817_1818del (p.His606fs)

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.1817_1818del (p.His606fs)

HGVS:

NC_000002.12:g.214745152_214745153del
NG_012047.3:g.69559_69560del
NM_000465.4:c.1817_1818delMANE SELECT
NM_001282543.2:c.1760_1761del
NM_001282545.2:c.464_465del
NM_001282548.2:c.407_408del
NM_001282549.2:c.365-14645_365-14644del
NP_000456.2:p.His606fs
NP_001269472.1:p.His587fs
NP_001269474.1:p.His155fs
NP_001269477.1:p.His136fs
LRG_297t1:c.1817_1818del
LRG_297:g.69559_69560del
LRG_297p1:p.His606fs
NC_000002.11:g.215609876_215609877del
NG_012047.2:g.69552_69553del
NM_000465.2:c.1817_1818del
NM_000465.2:c.1817_1818delAT
NM_000465.3:c.1817_1818del
NM_000465.3:c.1817_1818delAT
NR_104212.2:n.1782_1783del
NR_104215.2:n.1725_1726del
NR_104216.2:n.981_982del
p.H606RFS*6

Protein change:

H136fs

Links:

dbSNP: rs587782897

NCBI 1000 Genomes Browser:

rs587782897

Molecular consequence:

NM_000465.4:c.1817_1818del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282543.2:c.1760_1761del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282545.2:c.464_465del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282548.2:c.407_408del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001282549.2:c.365-14645_365-14644del - intron variant - [Sequence Ontology: SO:0001627]
NR_104212.2:n.1782_1783del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.1725_1726del - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.981_982del - 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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Gene ID:114207980

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000757238	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 27, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20077502, 21344236, 28492532
SCV004044965	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (May 24, 2023)	unknown	clinical testing	Citation Link,
SCV004217305	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 2, 2023)	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

SCV000757238

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 27, 2024)

germline

clinical testing

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

SCV004044965

Myriad Genetics, Inc.

criteria provided, single submitter

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

Pathogenic
(May 24, 2023)

unknown

clinical testing

Citation Link,

SCV004217305

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 2, 2023)

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

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, SCV000757238.7

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

Description

This sequence change creates a premature translational stop signal (p.His606Argfs*6) 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 variant has not been reported in the literature in individuals affected with BARD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 143017). 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

From Myriad Genetics, Inc., SCV004044965.2

#	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, SCV004217305.2

#	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: Oct 13, 2024

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