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NM_004281.4(BAG3):c.508-14_514del AND multiple conditions

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 10, 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:
RCV001966129.5

Allele description [Variation Report for NM_004281.4(BAG3):c.508-14_514del]

NM_004281.4(BAG3):c.508-14_514del

Gene:
BAG3:BAG cochaperone 3 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
10q26.11
Genomic location:
Preferred name:
NM_004281.4(BAG3):c.508-14_514del
HGVS:
  • NC_000010.11:g.119672241_119672261del
  • NG_016125.1:g.25872_25892del
  • NM_004281.4:c.508-14_514delMANE SELECT
  • LRG_742:g.25872_25892del
  • NC_000010.10:g.121431750_121431770del
  • NC_000010.10:g.121431753_121431773del
Links:
dbSNP: rs2134064890
NCBI 1000 Genomes Browser:
rs2134064890
Molecular consequence:
  • NM_004281.4:c.508-14_514del - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Myofibrillar myopathy 6
Synonyms:
Myofibrillar myopathy, BAG3-related
Identifiers:
MONDO: MONDO:0013061; MedGen: C2751831; Orphanet: 199340; OMIM: 612954
Name:
Dilated cardiomyopathy 1HH (CMD1HH)
Identifiers:
MONDO: MONDO:0013479; MedGen: C3151293; Orphanet: 154; OMIM: 613881

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002252176Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 10, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Genome-wide studies of copy number variation and exome sequencing identify rare variants in BAG3 as a cause of dilated cardiomyopathy.

Norton N, Li D, Rieder MJ, Siegfried JD, Rampersaud E, Züchner S, Mangos S, Gonzalez-Quintana J, Wang L, McGee S, Reiser J, Martin E, Nickerson DA, Hershberger RE.

Am J Hum Genet. 2011 Mar 11;88(3):273-82. doi: 10.1016/j.ajhg.2011.01.016. Epub 2011 Feb 25.

PubMed [citation]
PMID:
21353195
PMCID:
PMC3059419
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002252176.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has not been reported in the literature in individuals affected with BAG3-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant results in the deletion of part of exon 3 (c.508-14_514del) of the BAG3 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BAG3 are known to be pathogenic (PMID: 21353195, 25008357).

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

Last Updated: Feb 28, 2024