NM_000070.3(CAPN3):c.1745+4_1745+7del AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 6, 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:: RCV001058111.8

Allele description [Variation Report for NM_000070.3(CAPN3):c.1745+4_1745+7del]

NM_000070.3(CAPN3):c.1745+4_1745+7del

Gene:

CAPN3:calpain 3 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_000070.3(CAPN3):c.1745+4_1745+7del

HGVS:

NC_000015.10:g.42403002AGTG[1]
NG_008660.1:g.59900AGTG[1]
NM_000070.3:c.1745+4_1745+7delMANE SELECT
NM_024344.2:c.1745+4_1745+7del
NM_173087.2:c.1601+4_1601+7del
NM_173088.2:c.209+4_209+7del
LRG_849t1:c.1745+4_1745+7del
LRG_849:g.59900AGTG[1]
NC_000015.9:g.42695198_42695201del
NC_000015.9:g.42695200AGTG[1]
NM_000070.2:c.1745+4_1745+7del

Links:

dbSNP: rs794727082

NCBI 1000 Genomes Browser:

rs794727082

Molecular consequence:

NM_000070.3:c.1745+4_1745+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_024344.2:c.1745+4_1745+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_173087.2:c.1601+4_1601+7del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_173088.2:c.209+4_209+7del - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2A (LGMDR1)
Synonyms:: Limb-girdle muscular dystrophy, type 2A; Limb-girdle muscular dystrophy type 2; Muscular dystrophy, pelvofemoral; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009675; MedGen: C1869123; Orphanet: 267; OMIM: 253600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001222655	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 6, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17979987, 30564623, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001222655

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 6, 2022)

germline

clinical testing

PubMed (5)
[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

Transcriptional explorations of CAPN3 identify novel splicing mutations, a large-sized genomic deletion and evidence for messenger RNA decay.

Krahn M, Pécheux C, Chapon F, Béroud C, Drouin-Garraud V, Laforet P, Romero NB, Penisson-Besnier I, Bernard R, Urtizberea JA, Leturcq F, Lévy N.

Clin Genet. 2007 Dec;72(6):582-92. Epub 2007 Nov 1.

PubMed [citation]

PMID:: 17979987

Genetic landscape and novel disease mechanisms from a large LGMD cohort of 4656 patients.

Nallamilli BRR, Chakravorty S, Kesari A, Tanner A, Ankala A, Schneider T, da Silva C, Beadling R, Alexander JJ, Askree SH, Whitt Z, Bean L, Collins C, Khadilkar S, Gaitonde P, Dastur R, Wicklund M, Mozaffar T, Harms M, Rufibach L, Mittal P, Hegde M.

Ann Clin Transl Neurol. 2018 Dec;5(12):1574-1587. doi: 10.1002/acn3.649.

PubMed [citation]

PMID:: 30564623
PMCID:: PMC6292381

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001222655.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change falls in intron 13 of the CAPN3 gene. It does not directly change the encoded amino acid sequence of the CAPN3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs772774757, gnomAD 0.002%). This variant has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy (PMID: 17979987, 30564623). ClinVar contains an entry for this variant (Variation ID: 194149). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Oct 20, 2024

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