rs139879284
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 4P and 5B. PM1PM2BP4_StrongBP6
The NM_001130987.2(DYSF):c.5503C>T(p.Arg1835Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,613,924 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. R1835Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001130987.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.5503C>T | p.Arg1835Trp | missense_variant | 49/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.5386C>T | p.Arg1796Trp | missense_variant | 48/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.5503C>T | p.Arg1835Trp | missense_variant | 49/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.5386C>T | p.Arg1796Trp | missense_variant | 48/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00154 AC: 235AN: 152206Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000472 AC: 118AN: 250094Hom.: 0 AF XY: 0.000347 AC XY: 47AN XY: 135318
GnomAD4 exome AF: 0.000166 AC: 242AN: 1461600Hom.: 0 Cov.: 32 AF XY: 0.000154 AC XY: 112AN XY: 727078
GnomAD4 genome AF: 0.00154 AC: 235AN: 152324Hom.: 0 Cov.: 33 AF XY: 0.00133 AC XY: 99AN XY: 74476
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Jan 31, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Feb 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 14, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2020 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 21, 2023 | The c.5386C>T (p.R1796W) alteration is located in exon 48 (coding exon 48) of the DYSF gene. This alteration results from a C to T substitution at nucleotide position 5386, causing the arginine (R) at amino acid position 1796 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
DYSF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 03, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Qualitative or quantitative defects of dysferlin Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at