rs781777155
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001130987.2(DYSF):c.2594G>A(p.Arg865Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000675 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.2594G>A | p.Arg865Gln | missense_variant | 25/56 | ENST00000410020.8 | NP_001124459.1 | |
DYSF | NM_003494.4 | c.2540G>A | p.Arg847Gln | missense_variant | 25/55 | ENST00000258104.8 | NP_003485.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.2594G>A | p.Arg865Gln | missense_variant | 25/56 | 1 | NM_001130987.2 | ENSP00000386881.3 | ||
DYSF | ENST00000258104.8 | c.2540G>A | p.Arg847Gln | missense_variant | 25/55 | 1 | NM_003494.4 | ENSP00000258104.3 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251468Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135910
GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461886Hom.: 0 Cov.: 30 AF XY: 0.0000468 AC XY: 34AN XY: 727244
GnomAD4 genome AF: 0.0000526 AC: 8AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74300
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 07, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 847 of the DYSF protein (p.Arg847Gln). This variant is present in population databases (rs781777155, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. ClinVar contains an entry for this variant (Variation ID: 538636). 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 not expected to disrupt DYSF protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at