Variant: NM_000070.3(CAPN3):c.1800+21C>T

CA7511545

446978 (ClinVar)

Gene: CAPN3

Condition: autosomal recessive limb-girdle muscular dystrophy

Inheritance Mode: Autosomal recessive inheritance

UUID: af0c90fd-f673-40d4-9789-3324de606937

Approved on: 2025-01-09

Published on: 2025-01-09

HGVS expressions

NM_000070.3:c.1800+21C>T
NM_000070.3(CAPN3):c.1800+21C>T
NC_000015.10:g.42405964C>T
CM000677.2:g.42405964C>T
NC_000015.9:g.42698162C>T
CM000677.1:g.42698162C>T
NC_000015.8:g.40485454C>T
NG_008660.1:g.62862C>T
ENST00000337571.9:c.-82+996C>T
ENST00000349748.8:c.1638+2187C>T
ENST00000357568.8:c.1782+2187C>T
ENST00000397163.8:c.1800+21C>T
ENST00000397204.9:c.-82+21C>T
ENST00000466369.5:n.2291+2187C>T
ENST00000495723.1:n.2671+2187C>T
ENST00000549793.5:n.2013+2187C>T
ENST00000565173.2:n.174+1009C>T
ENST00000569136.6:c.-196+21C>T
ENST00000638141.2:n.1653+2187C>T
ENST00000673646.1:c.364+21C>T
ENST00000673692.1:c.-4+1113C>T
ENST00000673705.1:c.310-3339C>T
ENST00000673743.1:c.-437+1009C>T
ENST00000673750.1:c.-2442C>T
ENST00000673771.1:c.-196+996C>T
ENST00000673839.1:c.-340+1009C>T
ENST00000673851.1:c.-540+21C>T
ENST00000673854.1:n.1998C>T
ENST00000673886.1:c.-928-733C>T
ENST00000673890.1:c.-196+1009C>T
ENST00000673928.1:c.-340+1009C>T
ENST00000673936.1:c.-196+1113C>T
ENST00000673939.1:c.-82+1009C>T
ENST00000673978.1:c.-362+1009C>T
ENST00000673987.1:c.-196+21C>T
ENST00000674011.1:c.-196+1009C>T
ENST00000674012.1:n.75+996C>T
ENST00000674018.1:c.-540+996C>T
ENST00000674041.1:c.-82+1009C>T
ENST00000674052.1:c.24+21C>T
ENST00000674064.1:n.179+1009C>T
ENST00000674093.1:c.-82+1009C>T
ENST00000674119.1:c.-82+1113C>T
ENST00000674135.1:c.-132+1009C>T
ENST00000674139.1:c.-2442C>T
ENST00000674146.1:c.-524+21C>T
ENST00000674149.1:c.-524+1009C>T
ENST00000318023.11:c.1656+21C>T
ENST00000337571.8:c.-82+1009C>T
ENST00000349748.7:c.1638+2187C>T
ENST00000356316.7:c.-91+1000C>T
ENST00000357568.7:c.1782+2187C>T
ENST00000397163.7:c.1800+21C>T
ENST00000397200.8:c.264+21C>T
ENST00000397204.8:c.-82+21C>T
ENST00000561817.5:c.-82+1009C>T
ENST00000565173.1:n.129+1009C>T
ENST00000565274.5:c.12+21C>T
ENST00000565559.5:c.-132+21C>T
ENST00000567071.5:c.259+21C>T
ENST00000569136.5:c.-196+21C>T
ENST00000569827.5:c.246+2187C>T
NM_000070.2:c.1800+21C>T
NM_024344.1:c.1782+2187C>T
NM_173087.1:c.1638+2187C>T
NM_173088.1:c.264+21C>T
NM_173089.1:c.-82+1009C>T
NM_173090.1:c.-82+21C>T
NM_024344.2:c.1782+2187C>T
NM_173087.2:c.1638+2187C>T
NM_173088.2:c.264+21C>T
NM_173089.2:c.-82+1009C>T
NM_173090.2:c.-82+21C>T

Likely Benign

• Met criteria codes: BS1 BP7 BP4

• Not Met criteria codes: PM3

Expert Panel

Limb Girdle Muscular Dystrophy VCEP

Criteria Specification Information

Criteria Specification: ClinGen Limb Girdle Muscular Dystrophy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CAPN3 Version 1.0.0

Evidence submitted by expert panel

Limb Girdle Muscular Dystrophy VCEP

The NM_000070.3: c.1800+21C>T variant in CAPN3 is an intronic variant that does not occur in a splice region (+7/-21). The filtering allele frequency for this variant is 0.002152 for the European (non-Finnish) population in gnomAD v4.1.0 (the lower threshold of the 95% CI of 2461/1105660 exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold of 0.001 for BS1, and therefore meets this criterion (BS1). The SpliceAI prediction score for this variant is 0.01, which is less than the VCEP threshold of 0.05 (BP4, BP7). In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/09/2025): BS1, BP4, BP7.

Met criteria codes

• BS1: The filtering allele frequency for this variant is 0.002152 for the European (non-Finnish) population in gnomAD v4.1.0 (the lower threshold of the 95% CI of 2461/1105660 exome chromosomes), which is greater than the ClinGen LGMD VCEP threshold of 0.001 for BS1, and therefore meets this criterion (BS1).
• BP7: The SpliceAI prediction score for this variant is 0.01, which is less than the LGMD threshold of 0.05 (BP4, BP7).
• BP4: The SpliceAI prediction score for this variant is 0.01, which is less than the LGMD threshold of 0.05 (BP4, BP7).

Not Met criteria codes

• PM3: 2 single hit individuals in LOVD - not scoreable