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NM_000465.4(BARD1):c.425C>T (p.Ser142Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 22, 2024
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:
RCV000564493.5

Allele description [Variation Report for NM_000465.4(BARD1):c.425C>T (p.Ser142Leu)]

NM_000465.4(BARD1):c.425C>T (p.Ser142Leu)

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.425C>T (p.Ser142Leu)
HGVS:
  • NC_000002.12:g.214781449G>A
  • NG_012047.3:g.33263C>T
  • NM_000465.4:c.425C>TMANE SELECT
  • NM_001282543.2:c.368C>T
  • NM_001282545.2:c.215+15612C>T
  • NM_001282548.2:c.158+27963C>T
  • NM_001282549.2:c.364+10848C>T
  • NP_000456.2:p.Ser142Leu
  • NP_001269472.1:p.Ser123Leu
  • LRG_297t1:c.425C>T
  • LRG_297:g.33263C>T
  • LRG_297p1:p.Ser142Leu
  • NC_000002.11:g.215646173G>A
  • NG_012047.2:g.33256C>T
  • NM_000465.2:c.425C>T
  • NM_000465.3:c.425C>T
  • NR_104212.2:n.390C>T
  • NR_104215.2:n.333C>T
Protein change:
S123L
Links:
dbSNP: rs1553622692
NCBI 1000 Genomes Browser:
rs1553622692
Molecular consequence:
  • NM_001282545.2:c.215+15612C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001282548.2:c.158+27963C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001282549.2:c.364+10848C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000465.4:c.425C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282543.2:c.368C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104212.2:n.390C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104215.2:n.333C>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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000668212Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(May 22, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Ambry Genetics, SCV000668212.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The p.S142L variant (also known as c.425C>T), located in coding exon 4 of the BARD1 gene, results from a C to T substitution at nucleotide position 425. The serine at codon 142 is replaced by leucine, an amino acid with dissimilar properties. This alteration was identified in a cohort of 1040 individuals with advanced cancer diagnoses who underwent paired germline and tumor genetic testing (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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024