rs776452710
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The ENST00000410020.8(DYSF):āc.5210C>Gā(p.Pro1737Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,694 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P1737P) has been classified as Likely benign.
Frequency
Consequence
ENST00000410020.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.5210C>G | p.Pro1737Arg | missense_variant | 47/56 | ENST00000410020.8 | NP_001124459.1 | |
DYSF | NM_003494.4 | c.5093C>G | p.Pro1698Arg | missense_variant | 46/55 | ENST00000258104.8 | NP_003485.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.5210C>G | p.Pro1737Arg | missense_variant | 47/56 | 1 | NM_001130987.2 | ENSP00000386881 | A1 | |
DYSF | ENST00000258104.8 | c.5093C>G | p.Pro1698Arg | missense_variant | 46/55 | 1 | NM_003494.4 | ENSP00000258104 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251222Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135806
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461694Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727168
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Qualitative or quantitative defects of dysferlin Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 22, 2023 | This variant is present in population databases (rs776452710, gnomAD 0.003%). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function. ClinVar contains an entry for this variant (Variation ID: 567124). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (LGMD) (Invitae). It has also been observed to segregate with disease in related individuals. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1698 of the DYSF protein (p.Pro1698Arg). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Nov 13, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at