chr2-71644034-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001130987.2(DYSF):c.4597T>A(p.Tyr1533Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. Y1533H) 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 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.4597T>A | p.Tyr1533Asn | missense_variant | 42/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.4480T>A | p.Tyr1494Asn | missense_variant | 41/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.4597T>A | p.Tyr1533Asn | missense_variant | 42/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.4480T>A | p.Tyr1494Asn | missense_variant | 41/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1459826Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 725892
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 15, 2022 | 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. 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 expected to disrupt DYSF protein function. This variant has not been reported in the literature in individuals affected with DYSF-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1494 of the DYSF protein (p.Tyr1494Asn). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at