NM_000465.4(BARD1):c.127C>A (p.Arg43Ser) AND Familial cancer of breast

Germline classification:: Uncertain significance (4 submissions)
Last evaluated:: Mar 5, 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:: RCV000205388.14

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:: Familial cancer of breast
Synonyms:: Breast cancer, familial
Identifiers:: MONDO: MONDO:0016419; MedGen: C0346153; OMIM: 114480

Recent activity

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Gene Links for GEO Profiles (Select 79789915) (1)
Gene
C5orf15 chromosome 5 open reading frame 15 [Homo sapiens]
C5orf15 chromosome 5 open reading frame 15 [Homo sapiens]
Gene ID:56951

Gene
heterogeneous nuclear ribonucleoprotein F [Homo sapiens]
heterogeneous nuclear ribonucleoprotein F [Homo sapiens]
gi|148470402|ref|NP_001091675.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000260612	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 6, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000785517	Counsyl	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015))	Uncertain significance (Aug 31, 2017)	unknown	clinical testing	Counsyl_Autosomal_Dominant_Disease_Classification_criteria_(2015)_v1.pdf, Citation Link,
SCV004019286	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Uncertain significance (Feb 24, 2023)	unknown	clinical testing	Citation Link,
SCV004217194	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 5, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

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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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

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 Invitae, SCV000260612.10

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

Description

This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 43 of the BARD1 protein (p.Arg43Ser). This variant is present in population databases (rs752871324, gnomAD 0.03%). 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: 220225). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been 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

From Counsyl, SCV000785517.2

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

#	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 Myriad Genetics, Inc., SCV004019286.1

#	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 classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.

#	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, SCV004217194.2

#	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: Jun 17, 2024

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