NM_000070.3(CAPN3):c.1524+1G>T AND Autosomal recessive limb-girdle muscular dystrophy type 2A

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 3, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000669957.2

Allele description [Variation Report for NM_000070.3(CAPN3):c.1524+1G>T]

NM_000070.3(CAPN3):c.1524+1G>T

Gene:

CAPN3:calpain 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

15q15.1

Genomic location:

Preferred name:

NM_000070.3(CAPN3):c.1524+1G>T

HGVS:

NC_000015.10:g.42401811G>T
NG_008660.1:g.58709G>T
NM_000070.3:c.1524+1G>TMANE SELECT
NM_024344.2:c.1524+1G>T
NM_173087.2:c.1380+1G>T
LRG_849t1:c.1524+1G>T
LRG_849:g.58709G>T
NC_000015.9:g.42694009G>T
NM_000070.2:c.1524+1G>T

Links:

dbSNP: rs1275289254

NCBI 1000 Genomes Browser:

rs1275289254

Molecular consequence:

NM_000070.3:c.1524+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_024344.2:c.1524+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_173087.2:c.1380+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

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
SCV000794760	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Pathogenic (Oct 16, 2017)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 17258832, 26632398 Citation Link,
SCV002058240	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000794760

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Pathogenic
(Oct 16, 2017)

unknown

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV002058240

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 3, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Characterization of lobulated fibers in limb girdle muscular dystrophy type 2A by gene expression profiling.

Keira Y, Noguchi S, Kurokawa R, Fujita M, Minami N, Hayashi YK, Kato T, Nishino I.

Neurosci Res. 2007 Apr;57(4):513-21. Epub 2007 Jan 5.

PubMed [citation]

PMID:: 17258832

Clinical and Pathological Heterogeneity of Korean Patients with CAPN3 Mutations.

Park HJ, Jang H, Lee JH, Shin HY, Cho SR, Park KD, Bang D, Lee MG, Kim SM, Lee JH, Choi YC.

Yonsei Med J. 2016 Jan;57(1):173-9. doi: 10.3349/ymj.2016.57.1.173.

PubMed [citation]

PMID:: 26632398
PMCID:: PMC4696950

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000794760.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From 3billion, SCV002058240.1

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

Description

Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS). The variant has been reported to be associated with CAPN3 related disorder (ClinVar ID: VCV000554341). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000004, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Aug 5, 2023

ClinVar

Relating variation to medicine