rs763674597
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001130987.2(DYSF):c.3859G>T(p.Glu1287Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,204 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 (★★). Synonymous variant affecting the same amino acid position (i.e. E1287E) has been classified as Likely benign. 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
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3859G>T | p.Glu1287Ter | stop_gained | 34/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3805G>T | p.Glu1269Ter | stop_gained | 34/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3859G>T | p.Glu1287Ter | stop_gained | 34/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3805G>T | p.Glu1269Ter | stop_gained | 34/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 249890Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135286
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461018Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726874
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74336
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 18, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 09, 2018 | - - |
Miyoshi muscular dystrophy 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 16, 2024 | - - |
Qualitative or quantitative defects of dysferlin Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 23, 2023 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 558274). This premature translational stop signal has been observed in individual(s) with DYSF-related conditions (PMID: 17070050). This variant is present in population databases (rs763674597, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Glu1269*) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at