Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001130987.2(DYSF):c.1931T>C (p.Met644Thr)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA1705983

281014 (ClinVar)

Gene: DYSF

Condition: autosomal recessive limb-girdle muscular dystrophy

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: bcf6f4b6-7492-4e66-bd99-4d72bba5b8d8

Approved on: 2025-01-08

Published on: 2025-02-07

HGVS expressions

NM_001130987.2:c.1931T>C

NM_001130987.2(DYSF):c.1931T>C (p.Met644Thr)

NC_000002.12:g.71553135T>C

CM000664.2:g.71553135T>C

NC_000002.11:g.71780265T>C

CM000664.1:g.71780265T>C

NC_000002.10:g.71633773T>C

NG_008694.1:g.104513T>C

ENST00000258104.8:c.1877T>C

ENST00000410020.8:c.1931T>C

ENST00000258104.7:c.1877T>C

ENST00000394120.6:c.1880T>C

ENST00000409366.5:c.1880T>C

ENST00000409582.7:c.1928T>C

ENST00000409651.5:c.1973T>C

ENST00000409744.5:c.1838T>C

ENST00000409762.5:c.1928T>C

ENST00000410020.7:c.1931T>C

ENST00000410041.1:c.1931T>C

ENST00000413539.6:c.1970T>C

ENST00000429174.6:c.1877T>C

NM_001130455.1:c.1880T>C

NM_001130976.1:c.1835T>C

NM_001130977.1:c.1835T>C

NM_001130978.1:c.1877T>C

NM_001130979.1:c.1970T>C

NM_001130980.1:c.1928T>C

NM_001130981.1:c.1928T>C

NM_001130982.1:c.1973T>C

NM_001130983.1:c.1880T>C

NM_001130984.1:c.1838T>C

NM_001130985.1:c.1931T>C

NM_001130986.1:c.1838T>C

NM_001130987.1:c.1931T>C

NM_003494.3:c.1877T>C

NM_001130455.2:c.1880T>C

NM_001130976.2:c.1835T>C

NM_001130977.2:c.1835T>C

NM_001130978.2:c.1877T>C

NM_001130979.2:c.1970T>C

NM_001130980.2:c.1928T>C

NM_001130981.2:c.1928T>C

NM_001130982.2:c.1973T>C

NM_001130983.2:c.1880T>C

NM_001130984.2:c.1838T>C

NM_001130985.2:c.1931T>C

NM_001130986.2:c.1838T>C

NM_003494.4:c.1877T>C

Likely Benign

BS1

BP4

Evidence Links 0

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 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.1877T>C variant in DYSF, which is also known as NM_001130987.2: c.1931T>C p.(Met644Thr), is a missense variant predicted to cause substitution of methionine by threonine at amino acid 626 (p.Met626Thr). The filtering allele frequency of the variant is 0.002276 for European (non-Finnish) exome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 323/251362), which is higher than the VCEP threshold of 0.001 (BS1). The SpliceAI score for this variant is 0, suggesting it does not impact splicing. However, the computational predictor REVEL gives a score of 0.12, 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 Likely 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): BS1.

BS1

The filtering allele frequency of the variant is 0.002276 for European (non-Finnish) exome chromosomes in gnomAD v2.1.1 (the lower threshold of the 95% CI of 323/251362), which is higher than the VCEP threshold of 0.001 (BS1).

BP4

The SpliceAI score for this variant is 0, suggesting it does not impact splicing. However, the computational predictor REVEL gives a score of 0.12, 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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