NM_000465.4(BARD1):c.427A>G (p.Ile143Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 26, 2020
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:: RCV001199887.2

Allele description [Variation Report for NM_000465.4(BARD1):c.427A>G (p.Ile143Val)]

NM_000465.4(BARD1):c.427A>G (p.Ile143Val)

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.427A>G (p.Ile143Val)

HGVS:

NC_000002.12:g.214781447T>C
NG_012047.3:g.33265A>G
NM_000465.4:c.427A>GMANE SELECT
NM_001282543.2:c.370A>G
NM_001282545.2:c.215+15614A>G
NM_001282548.2:c.158+27965A>G
NM_001282549.2:c.364+10850A>G
NP_000456.2:p.Ile143Val
NP_001269472.1:p.Ile124Val
LRG_297t1:c.427A>G
LRG_297:g.33265A>G
LRG_297p1:p.Ile143Val
NC_000002.11:g.215646171T>C
NG_012047.2:g.33258A>G
NM_000465.2:c.427A>G
NM_000465.3:c.427A>G
NR_104212.2:n.392A>G
NR_104215.2:n.335A>G

Protein change:

I124V

Links:

dbSNP: rs1060501289

NCBI 1000 Genomes Browser:

rs1060501289

Molecular consequence:

NM_001282545.2:c.215+15614A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282548.2:c.158+27965A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001282549.2:c.364+10850A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000465.4:c.427A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.370A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.392A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.335A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV001370640	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (May 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001370640

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(May 26, 2020)

germline

clinical testing

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

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

Citations

PubMed

Functional analysis of clinical BARD1 germline variants.

Toh MR, Chong ST, Chan SH, Low CE, Ishak NDB, Lim JQ, Courtney E, Ngeow J.

Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4). doi:pii: a004093. 10.1101/mcs.a004093. Print 2019 Aug.

PubMed [citation]

PMID:: 31371347
PMCID:: PMC6672023

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001370640.1

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

Description

Variant summary: BARD1 c.427A>G (p.Ile143Val) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250406 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.427A>G has been reported in the literature (Toh_2019). This report however, does not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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 13, 2024

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