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.386G>A (p.Gly129Glu)

CA147747

94311 (ClinVar)

Gene: DYSF
Condition: autosomal recessive limb-girdle muscular dystrophy
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: b03f28b9-5b3e-4434-91fa-cbabf51daa42
Approved on: 2025-05-19
Published on: 2025-06-06

HGVS expressions

NM_001130987.2:c.386G>A
NM_001130987.2(DYSF):c.386G>A (p.Gly129Glu)
NC_000002.12:g.71511847G>A
CM000664.2:g.71511847G>A
NC_000002.11:g.71738977G>A
CM000664.1:g.71738977G>A
NC_000002.10:g.71592485G>A
NG_008694.1:g.63225G>A
ENST00000258104.8:c.383G>A
ENST00000410020.8:c.386G>A
ENST00000258104.7:c.383G>A
ENST00000394120.6:c.386G>A
ENST00000409366.5:c.386G>A
ENST00000409582.7:c.383G>A
ENST00000409651.5:c.386G>A
ENST00000409744.5:c.386G>A
ENST00000409762.5:c.383G>A
ENST00000410020.7:c.386G>A
ENST00000410041.1:c.386G>A
ENST00000413539.6:c.383G>A
ENST00000429174.6:c.383G>A
NM_001130455.1:c.386G>A
NM_001130976.1:c.383G>A
NM_001130977.1:c.383G>A
NM_001130978.1:c.383G>A
NM_001130979.1:c.383G>A
NM_001130980.1:c.383G>A
NM_001130981.1:c.383G>A
NM_001130982.1:c.386G>A
NM_001130983.1:c.386G>A
NM_001130984.1:c.386G>A
NM_001130985.1:c.386G>A
NM_001130986.1:c.386G>A
NM_001130987.1:c.386G>A
NM_003494.3:c.383G>A
NM_001130455.2:c.386G>A
NM_001130976.2:c.383G>A
NM_001130977.2:c.383G>A
NM_001130978.2:c.383G>A
NM_001130979.2:c.383G>A
NM_001130980.2:c.383G>A
NM_001130981.2:c.383G>A
NM_001130982.2:c.386G>A
NM_001130983.2:c.386G>A
NM_001130984.2:c.386G>A
NM_001130985.2:c.386G>A
NM_001130986.2:c.386G>A
NM_003494.4:c.383G>A
More

Benign

Met criteria codes 1
BA1
Not Met criteria codes 3
PM3 BP4 PP3

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.383G>A variant in DYSF, which is also known as NM_001130987.2: c.386G>A p.(Gly129Glu), is a missense variant predicted to cause substitution of glycine by glutamic acid at amino acid 128, p.(Gly128Glu). The Grpmax filtering allele frequency of this variant in gnomAD v4.1.0 is 0.03324 (the lower threshold of the 95% CI of 223/5988 Middle Eastern chromosomes), which is higher than the VCEP threshold of 0.003 (BA1). While this variant has been reported with a second heterozygous DYSF variant in an individual with reduced dysferlin expression (PMID: 21522182), its frequency in control populations is high relative to disease prevalence (PM3 not met). The SpliceAI score for this variant is 0.01, suggesting it does not impact splicing. The computational predictor REVEL gives a score of 0.45 (PP3 and 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; 05/19/2025): BA1.
Met criteria codes
BA1
The Grpmax filtering allele frequency of this variant is 0.03324 in gnomAD v4.1.0(the lower threshold of the 95% CI of 223/5988 Middle Eastern chromosomes), which is higher than the VCEP threshold of 0.003 (BA1). The Middle Eastern population is quite small, so I also confirmed that the threshold was also surpassed for the combined exome+genome data for the non-bottlenecked population with the highest MAF, the Admixed American, which gives an FAF of 0.004 (238/51016).
Not Met criteria codes
PM3
While this variant has been reported with a second heterozygous DYSF variant in an individual with reduced dysferlin expression (PMID: 21522182), its frequency in control populations is high relative to disease prevalence (PM3 not met).
BP4
The computational predictor REVEL gives a score of 0.45 (PP3 and BP4 not met).
PP3
The computational predictor REVEL gives a score of 0.45 (PP3 and BP4 not met).
Curation History
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