Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene label mismatch: DYSF vs undefined
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001130987.2(DYSF):c.3588C>T (p.Ile1196=)

CA152665

94307 (ClinVar)

Gene: DYSF
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 1acb4353-068f-4367-a82f-b87edeacdbb3
Approved on: 2025-05-19
Published on: 2025-06-06

HGVS expressions

NM_001130987.2:c.3588C>T
NM_001130987.2(DYSF):c.3588C>T (p.Ile1196=)
NC_000002.12:g.71598577C>T
CM000664.2:g.71598577C>T
NC_000002.11:g.71825707C>T
CM000664.1:g.71825707C>T
NC_000002.10:g.71679215C>T
NG_008694.1:g.149955C>T
ENST00000698057.1:c.960C>T
ENST00000698058.1:c.177C>T
ENST00000698059.1:c.177C>T
ENST00000258104.8:c.3534C>T
ENST00000410020.8:c.3588C>T
ENST00000258104.7:c.3534C>T
ENST00000394120.6:c.3537C>T
ENST00000409366.5:c.3537C>T
ENST00000409582.7:c.3585C>T
ENST00000409651.5:c.3630C>T
ENST00000409744.5:c.3495C>T
ENST00000409762.5:c.3585C>T
ENST00000410020.7:c.3588C>T
ENST00000410041.1:c.3588C>T
ENST00000413539.6:c.3627C>T
ENST00000429174.6:c.3534C>T
ENST00000475076.5:n.362C>T
ENST00000479049.6:n.419C>T
ENST00000493767.1:n.255C>T
NM_001130455.1:c.3537C>T
NM_001130976.1:c.3492C>T
NM_001130977.1:c.3492C>T
NM_001130978.1:c.3534C>T
NM_001130979.1:c.3627C>T
NM_001130980.1:c.3585C>T
NM_001130981.1:c.3585C>T
NM_001130982.1:c.3630C>T
NM_001130983.1:c.3537C>T
NM_001130984.1:c.3495C>T
NM_001130985.1:c.3588C>T
NM_001130986.1:c.3495C>T
NM_001130987.1:c.3588C>T
NM_003494.3:c.3534C>T
NM_001130455.2:c.3537C>T
NM_001130976.2:c.3492C>T
NM_001130977.2:c.3492C>T
NM_001130978.2:c.3534C>T
NM_001130979.2:c.3627C>T
NM_001130980.2:c.3585C>T
NM_001130981.2:c.3585C>T
NM_001130982.2:c.3630C>T
NM_001130983.2:c.3537C>T
NM_001130984.2:c.3495C>T
NM_001130985.2:c.3588C>T
NM_001130986.2:c.3495C>T
NM_003494.4:c.3534C>T
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 3
BP4 BP7 PM3

Evidence Links 0

Expert Panel

Criteria Specification Information

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Limb Girdle Muscular Dystrophy VCEP
The NM_003494.4: c.3534C>T p.(Ile1178=) variant in DYSF, which is also known as NM_001130987.2: c.3588C>T (p.Ile1196=), is a synonymous (silent) variant that is not located in a splice region (outside of the first and the last 3 bases of the exon). The filtering allele frequency for this variant is 0.008874 in gnomAD v4.1.0 (the lower threshold of the 95% CI of 10642/1180038 European (non-Finnish) chromosomes), which is higher than the VCEP threshold of 0.003 (BA1). This variant was detected in a heterozygous state in one individual with suspected LGMD and absent dysferlin expression by blood monocyte assay. No second variant in DYSF was identified, and this individual also had two variants in DNAJB6 (PMID: 25493284, 36983702). The SpliceAI prediction score for this variant is 0.27, which is greater than the VCEP threshold of <0.05 (BP4 not met). However, RNASeq data showed this variant does not affect splicing (PMID: 36983702). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 05/19/2025): BA1.
Met criteria codes
BA1
The filtering allele frequency for this variant is 0.008874 in gnomAD v4.1.0 (the lower threshold of the 95% CI of 10642/1180038 European (non-Finnish) chromosomes), which is higher than the VCEP threshold of 0.003 (BA1).
Not Met criteria codes
BP4
The SpliceAI prediction score for this variant is 0.27 for acceptor loss, which is greater than the VCEP threshold of <0.05 (BP4 not met).
BP7
RNASeq data showed this variant does not affect splicing (PMID: 36983702). However, the splice AI score is above the threshold.
PM3
The variant was detected in a heterozygous state in one individual with suspected LGMD and absent dysferlin expression by blood monocyte assay. No second variant was identified in DYSF, and this individual also had two variants in DNAJB6 (PMID: 25493284, 36983702).
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.