NM_000465.4(BARD1):c.127C>A (p.Arg43Ser) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 10, 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:: RCV000215506.10

Allele description [Variation Report for NM_000465.4(BARD1):c.127C>A (p.Arg43Ser)]

NM_000465.4(BARD1):c.127C>A (p.Arg43Ser)

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.127C>A (p.Arg43Ser)

HGVS:

NC_000002.12:g.214809443G>T
NG_012047.3:g.5269C>A
NM_000465.4:c.127C>AMANE SELECT
NM_001282543.2:c.127C>A
NM_001282545.2:c.127C>A
NM_001282548.2:c.127C>A
NM_001282549.2:c.127C>A
NP_000456.2:p.Arg43Ser
NP_001269472.1:p.Arg43Ser
NP_001269474.1:p.Arg43Ser
NP_001269477.1:p.Arg43Ser
NP_001269478.1:p.Arg43Ser
LRG_297t1:c.127C>A
LRG_297:g.5269C>A
LRG_297p1:p.Arg43Ser
NC_000002.11:g.215674167G>T
NG_012047.2:g.5262C>A
NM_000465.2:c.127C>A
NM_000465.3:c.127C>A
NR_104212.2:n.241C>A
NR_104215.2:n.241C>A
NR_104216.2:n.241C>A

Protein change:

R43S

Links:

dbSNP: rs752871324

NCBI 1000 Genomes Browser:

rs752871324

Molecular consequence:

NM_000465.4:c.127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.127C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.127C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.241C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.241C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.241C>A - 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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000275668	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Jan 10, 2024)	germline	clinical testing	Citation Link,
SCV000682680	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 21, 2020)	germline	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

SCV000275668

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Jan 10, 2024)

germline

clinical testing

Citation Link,

SCV000682680

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 21, 2020)

germline

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ambry Genetics, SCV000275668.7

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

Description

The p.R43S variant (also known as c.127C>A), located in coding exon 1 of the BARD1 gene, results from a C to A substitution at nucleotide position 127. The arginine at codon 43 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 Color Diagnostics, LLC DBA Color Health, SCV000682680.4

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

Description

This missense variant replaces arginine with serine at codon 43 of the BARD1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 8/272102 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of 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: Sep 29, 2024

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