rs778092738
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001130987.2(DYSF):c.4042C>T(p.Gln1348*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001130987.2 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.4042C>T | p.Gln1348* | stop_gained | Exon 37 of 56 | 1 | NM_001130987.2 | ENSP00000386881.3 | ||
DYSF | ENST00000258104.8 | c.3988C>T | p.Gln1330* | stop_gained | Exon 37 of 55 | 1 | NM_003494.4 | ENSP00000258104.3 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461654Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727112
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
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Autosomal recessive limb-girdle muscular dystrophy type 2B Pathogenic:1
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Qualitative or quantitative defects of dysferlin Pathogenic:1
This sequence change creates a premature translational stop signal (p.Gln1330*) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with dysferlinopathy (PMID: 25591676, 27647186, 30107846). ClinVar contains an entry for this variant (Variation ID: 554013). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at