rs763456750
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_001130987.2(DYSF):c.2393G>A(p.Arg798His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000731 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R798C) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.2393G>A | p.Arg798His | missense_variant | 23/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.2339G>A | p.Arg780His | missense_variant | 23/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.2393G>A | p.Arg798His | missense_variant | 23/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.2339G>A | p.Arg780His | missense_variant | 23/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152186Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000400 AC: 10AN: 249924Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135166
GnomAD4 exome AF: 0.0000732 AC: 107AN: 1461644Hom.: 0 Cov.: 32 AF XY: 0.0000770 AC XY: 56AN XY: 727098
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152186Hom.: 0 Cov.: 33 AF XY: 0.0000807 AC XY: 6AN XY: 74340
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 04, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Qualitative or quantitative defects of dysferlin Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at