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NM_000465.4(BARD1):c.1127C>T (p.Ser376Leu) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 15, 2022
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:
RCV001251335.3

Allele description [Variation Report for NM_000465.4(BARD1):c.1127C>T (p.Ser376Leu)]

NM_000465.4(BARD1):c.1127C>T (p.Ser376Leu)

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.1127C>T (p.Ser376Leu)
HGVS:
  • NC_000002.12:g.214780747G>A
  • NG_012047.3:g.33965C>T
  • NM_000465.4:c.1127C>TMANE SELECT
  • NM_001282543.2:c.1070C>T
  • NM_001282545.2:c.215+16314C>T
  • NM_001282548.2:c.159-28192C>T
  • NM_001282549.2:c.364+11550C>T
  • NP_000456.2:p.Ser376Leu
  • NP_001269472.1:p.Ser357Leu
  • LRG_297t1:c.1127C>T
  • LRG_297:g.33965C>T
  • LRG_297p1:p.Ser376Leu
  • NC_000002.11:g.215645471G>A
  • NG_012047.2:g.33958C>T
  • NM_000465.2:c.1127C>T
  • NM_000465.3:c.1127C>T
  • NR_104212.2:n.1092C>T
  • NR_104215.2:n.1035C>T
  • p.S376L
Protein change:
S357L
Links:
dbSNP: rs587782333
NCBI 1000 Genomes Browser:
rs587782333
Molecular consequence:
  • NM_001282545.2:c.215+16314C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001282548.2:c.159-28192C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001282549.2:c.364+11550C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000465.4:c.1127C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282543.2:c.1070C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104212.2:n.1092C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104215.2:n.1035C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001426897Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Dec 15, 2022) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Germline Mutations in the BRIP1, BARD1, PALB2, and NBN Genes in Women With Ovarian Cancer.

Ramus SJ, Song H, Dicks E, Tyrer JP, Rosenthal AN, Intermaggio MP, Fraser L, Gentry-Maharaj A, Hayward J, Philpott S, Anderson C, Edlund CK, Conti D, Harrington P, Barrowdale D, Bowtell DD, Alsop K, Mitchell G; AOCS Study Group., Cicek MS, Cunningham JM, Fridley BL, et al.

J Natl Cancer Inst. 2015 Aug 27;107(11). doi:pii: djv214. 10.1093/jnci/djv214. Print 2015 Nov.

PubMed [citation]
PMID:
26315354
PMCID:
PMC4643629

Analysis of hereditary cancer syndromes by using a panel of genes: novel and multiple pathogenic mutations.

Tsaousis GN, Papadopoulou E, Apessos A, Agiannitopoulos K, Pepe G, Kampouri S, Diamantopoulos N, Floros T, Iosifidou R, Katopodi O, Koumarianou A, Markopoulos C, Papazisis K, Venizelos V, Xanthakis I, Xepapadakis G, Banu E, Eniu DT, Negru S, Stanculeanu DL, Ungureanu A, Ozmen V, et al.

BMC Cancer. 2019 Jun 3;19(1):535. doi: 10.1186/s12885-019-5756-4.

PubMed [citation]
PMID:
31159747
PMCID:
PMC6547505
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001426897.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: BARD1 c.1127C>T (p.Ser376Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 251330 control chromosomes, predominantly at a frequency of 0.00013 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not higher than predicted for a pathogenic variant in BARD1 causing Breast Cancer (6.4e-05 vs 0.00025), allowing no conclusion about variant significance. c.1127C>T has been reported in the literature in individuals who underwent genetic testing for familial cancers (e.g. Tsaousis_2019), but also in healthy controls (e.g. Ramus_2015). These reports do not provide unequivocal conclusions about association of the variant with Breast Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=5) and likely benign (n=2) . Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: May 7, 2024