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 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.4046G>T (p.Arg1349Leu)

CA147753

94315 (ClinVar)

Gene: DYSF
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: ae86deec-ad2c-4930-a11f-0cb27bb536d5
Approved on: 2025-01-08
Published on: 2025-01-08

HGVS expressions

NM_001130987.2:c.4046G>T
NM_001130987.2(DYSF):c.4046G>T (p.Arg1349Leu)
NC_000002.12:g.71611333G>T
CM000664.2:g.71611333G>T
NC_000002.11:g.71838463G>T
CM000664.1:g.71838463G>T
NC_000002.10:g.71691971G>T
NG_008694.1:g.162711G>T
ENST00000698057.1:c.1460G>T
ENST00000698058.1:c.677G>T
ENST00000698059.1:c.635G>T
ENST00000258104.8:c.3992G>T
ENST00000410020.8:c.4046G>T
ENST00000258104.7:c.3992G>T
ENST00000394120.6:c.3995G>T
ENST00000409366.5:c.3995G>T
ENST00000409582.7:c.4043G>T
ENST00000409651.5:c.4088G>T
ENST00000409744.5:c.3953G>T
ENST00000409762.5:c.4043G>T
ENST00000410020.7:c.4046G>T
ENST00000410041.1:c.4046G>T
ENST00000413539.6:c.4085G>T
ENST00000429174.6:c.3992G>T
ENST00000468173.1:n.228G>T
ENST00000472873.5:n.376G>T
ENST00000479049.6:n.877G>T
ENST00000487180.5:n.211G>T
ENST00000494501.5:n.352G>T
NM_001130455.1:c.3995G>T
NM_001130976.1:c.3950G>T
NM_001130977.1:c.3950G>T
NM_001130978.1:c.3992G>T
NM_001130979.1:c.4085G>T
NM_001130980.1:c.4043G>T
NM_001130981.1:c.4043G>T
NM_001130982.1:c.4088G>T
NM_001130983.1:c.3995G>T
NM_001130984.1:c.3953G>T
NM_001130985.1:c.4046G>T
NM_001130986.1:c.3953G>T
NM_001130987.1:c.4046G>T
NM_003494.3:c.3992G>T
NM_001130455.2:c.3995G>T
NM_001130976.2:c.3950G>T
NM_001130977.2:c.3950G>T
NM_001130978.2:c.3992G>T
NM_001130979.2:c.4085G>T
NM_001130980.2:c.4043G>T
NM_001130981.2:c.4043G>T
NM_001130982.2:c.4088G>T
NM_001130983.2:c.3995G>T
NM_001130984.2:c.3953G>T
NM_001130985.2:c.4046G>T
NM_001130986.2:c.3953G>T
NM_003494.4:c.3992G>T
More

Benign

Met criteria codes 2
BP2 BA1
Not Met criteria codes 1
BP4

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.3992G>T variant in DYSF, which is also known as NM_001130987.2: c.4046G>T p.(Arg1349Leu), is a missense variant predicted to cause substitution of arginine by leucine at amino acid 1331 (p.Arg1331Leu). The filtering allele frequency of the variant is 0.03441 for European (non-Finnish) genome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 943/31374), which is higher than the VCEP threshold of 0.003 (BA1). This variant has also been observed in cis with the variant c.5836_5839del p.(Gln1946TrpfsTer19), which is classified as pathogenic by the ClinGen LGMD VCEP (PMID: 19528035) (BP2). The SpliceAI score for this variant is 0, suggesting it does not impact splicing. However, the computational predictor REVEL gives a score of 0.39, which is above the LGMD VCEP threshold predicting a benign impact on DYSF function (≤0.1; BP4 not met). 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; 01/08/2025): BA1, BP2.
Met criteria codes
BP2
This variant has also been observed in cis with the variant c.5836_5839del p.(Gln1946TrpfsTer19), which is classified as pathogenic by the ClinGen LGMD VCEP (PMID: 19528035) (BP2).
BA1
The filtering allele frequency of the variant is 0.03441 for European (non-Finnish) genome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 943/31374), which is higher than the VCEP threshold of 0.003 (BA1).
Not Met criteria codes
BP4
The SpliceAI score for this variant is 0, suggesting it does not impact splicing. However, the computational predictor REVEL gives a score of 0.39, which is above the LGMD VCEP threshold predicting a benign impact on DYSF function (≤0.1; BP4 not met).
Curation History
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