NM_000465.4(BARD1):c.111T>A (p.Ser37Arg) AND Malignant tumor of breast

Germline classification:: Uncertain significance (1 submission)
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001357501.2

Allele description [Variation Report for NM_000465.4(BARD1):c.111T>A (p.Ser37Arg)]

NM_000465.4(BARD1):c.111T>A (p.Ser37Arg)

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.111T>A (p.Ser37Arg)

HGVS:

NC_000002.12:g.214809459A>T
NG_012047.3:g.5253T>A
NM_000465.4:c.111T>AMANE SELECT
NM_001282543.2:c.111T>A
NM_001282545.2:c.111T>A
NM_001282548.2:c.111T>A
NM_001282549.2:c.111T>A
NP_000456.2:p.Ser37Arg
NP_001269472.1:p.Ser37Arg
NP_001269474.1:p.Ser37Arg
NP_001269477.1:p.Ser37Arg
NP_001269478.1:p.Ser37Arg
LRG_297t1:c.111T>A
LRG_297:g.5253T>A
LRG_297p1:p.Ser37Arg
NC_000002.11:g.215674183A>T
NR_104212.2:n.225T>A
NR_104215.2:n.225T>A
NR_104216.2:n.225T>A

Protein change:

S37R

Links:

dbSNP: rs2106171106

NCBI 1000 Genomes Browser:

rs2106171106

Molecular consequence:

NM_000465.4:c.111T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.111T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.111T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.111T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.111T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.225T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.225T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.225T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Malignant tumor of breast
Synonyms:: Malignant breast neoplasm; Cancer breast
Identifiers:: MONDO: MONDO:0007254; MedGen: C0006142

Recent activity

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rho guanine nucleotide exchange factor 9 isoform 4 [Homo sapiens]
rho guanine nucleotide exchange factor 9 isoform 4 [Homo sapiens]
gi|1591612745|ref|NP_001355966.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001552987	Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR) See additional submitters Franklin by Genoox	no assertion criteria provided	Uncertain significance	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001552987

Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided

Uncertain significance

unknown

clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552987.1

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

Description

The BARD1 p.Ser37Arg variant was not identified in the literature nor was it identified in the following databases: dbSNP, ClinVar, Cosmic, MutDB, Zhejiang Colon Cancer Database, databases, the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Ser37 residue is conserved in mammals but not in more distantly related organisms, and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. 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	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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