rs766936914
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The ENST00000410020.8(DYSF):βc.1350delβ(p.Phe451LeufsTer41) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,836 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. D449D) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
ENST00000410020.8 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.1350del | p.Phe451LeufsTer41 | frameshift_variant | 14/56 | ENST00000410020.8 | NP_001124459.1 | |
DYSF | NM_003494.4 | c.1254del | p.Phe419LeufsTer41 | frameshift_variant | 13/55 | ENST00000258104.8 | NP_003485.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.1350del | p.Phe451LeufsTer41 | frameshift_variant | 14/56 | 1 | NM_001130987.2 | ENSP00000386881 | A1 | |
DYSF | ENST00000258104.8 | c.1254del | p.Phe419LeufsTer41 | frameshift_variant | 13/55 | 1 | NM_003494.4 | ENSP00000258104 | A1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251376Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135860
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461836Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727206
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2B Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Counsyl | May 04, 2017 | - - |
Miyoshi muscular dystrophy 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Jan 10, 2023 | - - |
Qualitative or quantitative defects of dysferlin Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 14, 2022 | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 551669). This variant is also known as Pro418ProfsX123. This premature translational stop signal has been observed in individual(s) with clinical features of limb-girdle muscular dystrophy and/or dysferlinopathy (PMID: 17994539, 27647186). This variant is present in population databases (rs766936914, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Phe419Leufs*41) in the DYSF gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYSF are known to be pathogenic (PMID: 17698709, 20301480). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at