NM_000465.4(BARD1):c.365-8del AND not specified

Germline classification:: Benign (2 submissions)
Last evaluated:: Mar 21, 2021
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:: RCV000478554.3

Allele description [Variation Report for NM_000465.4(BARD1):c.365-8del]

NM_000465.4(BARD1):c.365-8del

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.365-8del

HGVS:

NC_000002.12:g.214781523del
NG_012047.3:g.33195del
NM_000465.4:c.365-8delMANE SELECT
NM_001282543.2:c.308-8del
NM_001282545.2:c.215+15544del
NM_001282548.2:c.158+27895del
NM_001282549.2:c.364+10780del
LRG_297t1:c.365-8del
LRG_297:g.33195del
NC_000002.11:g.215646241del
NC_000002.11:g.215646247del
NG_012047.2:g.33188del
NM_000465.2:c.365-8delT
NM_000465.3:c.365-8del
NM_000465.3:c.365-8delT

Links:

dbSNP: rs776103948

NCBI 1000 Genomes Browser:

rs776103948

Molecular consequence:

NM_000465.4:c.365-8del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282543.2:c.308-8del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282545.2:c.215+15544del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+27895del - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+10780del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000564691	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Mar 17, 2015)	germline	clinical testing	Citation Link,
SCV001554515	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 21, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000564691

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Benign
(Mar 17, 2015)

germline

clinical testing

Citation Link,

SCV001554515

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Benign
(Mar 21, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV000564691.4

#	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 likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001554515.1

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

Description

Variant summary: BARD1 c.365-8delT alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8.4e-05 in 238706 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BARD1 causing Breast Cancer (8.4e-05 vs 0.00025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.365-8delT in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.

#	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: Oct 20, 2024

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