2-71574366-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001130987.2(DYSF):c.3397G>A(p.Ala1133Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000558 in 1,613,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 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. A1133S) 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.3397G>A | p.Ala1133Thr | missense_variant | 30/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3343G>A | p.Ala1115Thr | missense_variant | 30/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3397G>A | p.Ala1133Thr | missense_variant | 30/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3343G>A | p.Ala1115Thr | missense_variant | 30/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152240Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250912Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135586
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461230Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6AN XY: 726806
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152358Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74512
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 25, 2020 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 28, 2022 | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1115 of the DYSF protein (p.Ala1115Thr). This variant is present in population databases (rs200334333, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with DYSF-related conditions. 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