NM_000465.4(BARD1):c.59C>T (p.Pro20Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 14, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000774689.10

Allele description [Variation Report for NM_000465.4(BARD1):c.59C>T (p.Pro20Leu)]

NM_000465.4(BARD1):c.59C>T (p.Pro20Leu)

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.59C>T (p.Pro20Leu)

HGVS:

NC_000002.12:g.214809511G>A
NG_012047.3:g.5201C>T
NM_000465.4:c.59C>TMANE SELECT
NM_001282543.2:c.59C>T
NM_001282545.2:c.59C>T
NM_001282548.2:c.59C>T
NM_001282549.2:c.59C>T
NP_000456.2:p.Pro20Leu
NP_001269472.1:p.Pro20Leu
NP_001269474.1:p.Pro20Leu
NP_001269477.1:p.Pro20Leu
NP_001269478.1:p.Pro20Leu
LRG_297t1:c.59C>T
LRG_297:g.5201C>T
LRG_297p1:p.Pro20Leu
NC_000002.11:g.215674235G>A
NG_012047.2:g.5194C>T
NM_000465.2:c.59C>T
NM_000465.3:c.59C>T
NR_104212.2:n.173C>T
NR_104215.2:n.173C>T
NR_104216.2:n.173C>T

Protein change:

P20L

Links:

dbSNP: rs753686197

NCBI 1000 Genomes Browser:

rs753686197

Molecular consequence:

NM_000465.4:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282543.2:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282545.2:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282548.2:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001282549.2:c.59C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_104212.2:n.173C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104215.2:n.173C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_104216.2:n.173C>T - 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
SCV000908596	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jul 29, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001186857	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 14, 2022)	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

SCV000908596

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jul 29, 2021)

germline

clinical testing

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

SCV001186857

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 14, 2022)

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

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

Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing.

Mandelker D, Zhang L, Kemel Y, Stadler ZK, Joseph V, Zehir A, Pradhan N, Arnold A, Walsh MF, Li Y, Balakrishnan AR, Syed A, Prasad M, Nafa K, Carlo MI, Cadoo KA, Sheehan M, Fleischut MH, Salo-Mullen E, Trottier M, Lipkin SM, Lincoln A, et al.

JAMA. 2017 Sep 5;318(9):825-835. doi: 10.1001/jama.2017.11137. Erratum in: JAMA. 2018 Dec 11;320(22):2381. doi: 10.1001/jama.2018.17511.

PubMed [citation]

PMID:: 28873162
PMCID:: PMC5611881

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000908596.3

#	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	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Ambry Genetics, SCV001186857.4

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

Description

The p.P20L variant (also known as c.59C>T), located in coding exon 1 of the BARD1 gene, results from a C to T substitution at nucleotide position 59. The proline at codon 20 is replaced by leucine, an amino acid with similar properties. This alteration has been observed in a cohort of 1040 patients with advanced cancer who were tested for germline mutations in 76 cancer predisposition genes, but specific clinical information was not provided (Mandelker D et al. JAMA. 2017 09;318:825-835). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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

Last Updated: Sep 29, 2024

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