rs761302882
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001130987.2(DYSF):c.1149+4A>G variant causes a splice region, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001130987.2 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.1149+4A>G | splice_region_variant, intron_variant | 1 | NM_001130987.2 | ENSP00000386881.3 | ||||
DYSF | ENST00000258104.8 | c.1053+4A>G | splice_region_variant, intron_variant | 1 | NM_003494.4 | ENSP00000258104.3 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251424Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135896
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461668Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727154
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 17, 2016 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 10, 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 288116). This variant has been observed in individual(s) with clinical features of DYSF-related conditions (PMID: 25312915, 30564623; Invitae). This variant is present in population databases (rs761302882, gnomAD 0.01%). This sequence change falls in intron 11 of the DYSF gene. It does not directly change the encoded amino acid sequence of the DYSF protein. It affects a nucleotide within the consensus splice site. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at