2-71574300-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001130987.2(DYSF):c.3331C>T(p.Arg1111Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000855 in 1,613,990 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1111H) 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3331C>T | p.Arg1111Cys | missense_variant | 30/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3277C>T | p.Arg1093Cys | missense_variant | 30/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3331C>T | p.Arg1111Cys | missense_variant | 30/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3277C>T | p.Arg1093Cys | missense_variant | 30/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 251016Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135748
GnomAD4 exome AF: 0.0000903 AC: 132AN: 1461746Hom.: 1 Cov.: 33 AF XY: 0.0000976 AC XY: 71AN XY: 727168
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152244Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74380
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 15, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 27, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 21, 2022 | The c.3277C>T (p.R1093C) alteration is located in exon 30 (coding exon 30) of the DYSF gene. This alteration results from a C to T substitution at nucleotide position 3277, causing the arginine (R) at amino acid position 1093 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 12, 2020 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 19, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1093 of the DYSF protein (p.Arg1093Cys). This variant is present in population databases (rs372817333, gnomAD 0.008%). 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: 288793). 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. 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