rs761528558
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001130987.2(DYSF):c.3493G>A(p.Asp1165Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,613,844 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. D1165H) 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.3493G>A | p.Asp1165Asn | missense_variant | 31/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3439G>A | p.Asp1147Asn | missense_variant | 31/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3493G>A | p.Asp1165Asn | missense_variant | 31/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3439G>A | p.Asp1147Asn | missense_variant | 31/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251486Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135918
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461714Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727174
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74308
ClinVar
Submissions by phenotype
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 | Invitae | Dec 06, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1147 of the DYSF protein (p.Asp1147Asn). This variant is present in population databases (rs761528558, gnomAD 0.006%). 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: 471298). 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 with a negative predictive value of 95%. 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