NM_004281.4(BAG3):c.100_107del (p.Thr34fs) AND Primary dilated cardiomyopathy

Clinical significance:Likely pathogenic (Last evaluated: Mar 23, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000156812.2

Allele description [Variation Report for NM_004281.4(BAG3):c.100_107del (p.Thr34fs)]

NM_004281.4(BAG3):c.100_107del (p.Thr34fs)

Gene:
BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
10q26.11
Genomic location:
Preferred name:
NM_004281.4(BAG3):c.100_107del (p.Thr34fs)
HGVS:
  • NC_000010.11:g.119651775_119651782del
  • NG_016125.1:g.5406_5413del
  • NM_004281.4:c.100_107delMANE SELECT
  • NP_004272.2:p.Thr34fs
  • LRG_742:g.5406_5413del
  • NC_000010.10:g.121411287_121411294del
  • NC_000010.10:g.121411287_121411294delACCGGCTG
  • NM_004281.3:c.100_107delACCGGCTG
  • p.Thr34AlafsX21
Protein change:
T34fs
Links:
dbSNP: rs727505283
NCBI 1000 Genomes Browser:
rs727505283
Molecular consequence:
  • NM_004281.4:c.100_107del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Primary dilated cardiomyopathy (DCM)
Synonyms:
Dilated Cardiomyopathy
Identifiers:
EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000206533Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(Mar 23, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided41not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000206533.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (1)

Description

The p.Thr34AlafsX21 variant in BAG3 has been identified in 2 siblings with DCM ( LMM data) and was absent from large population studies, though the ability of th ese studies to accurately detect indels may be limited. This variant is predicte d to cause a frameshift, which alters the protein?s amino acid sequence beginnin g at position 34 and leads to a premature termination codon 21 amino acids downs tream. This alteration is then predicted to lead to a truncated or absent protei n. Loss-of-function variants in BAG3 have been reported to be disease-causing (K nezevic 2015). In summary, although additional studies are required to fully est ablish its clinical significance, the p.Thr34AlafsX21 variant is likely pathogen ic. ACMG/AMP Criteria applied: PVS1_Strong, PM2.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided4not provided1not provided

Last Updated: Nov 20, 2021

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