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:: RCV001966129.6

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002252176	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jun 10, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 21353195, 25008357, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002252176

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jun 10, 2022)

germline

clinical testing

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

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

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002252176.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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).

#	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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