rs76402294
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2
The NM_001130987.2(DYSF):c.1577-1635C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 1,610,416 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001130987.2 intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.1577-1635C>G | intron_variant | Intron 17 of 55 | 1 | NM_001130987.2 | ENSP00000386881.3 | |||
DYSF | ENST00000258104.8 | c.1522+15C>G | intron_variant | Intron 17 of 54 | 1 | NM_003494.4 | ENSP00000258104.3 |
Frequencies
GnomAD3 genomes AF: 0.0288 AC: 4371AN: 151992Hom.: 88 Cov.: 31
GnomAD3 exomes AF: 0.0212 AC: 5197AN: 244708Hom.: 64 AF XY: 0.0202 AC XY: 2666AN XY: 132248
GnomAD4 exome AF: 0.0212 AC: 30942AN: 1458306Hom.: 379 Cov.: 31 AF XY: 0.0204 AC XY: 14822AN XY: 725100
GnomAD4 genome AF: 0.0288 AC: 4382AN: 152110Hom.: 88 Cov.: 31 AF XY: 0.0291 AC XY: 2164AN XY: 74354
ClinVar
Submissions by phenotype
not specified Benign:3
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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not provided Benign:3
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Qualitative or quantitative defects of dysferlin Benign:2
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This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Limb-girdle muscular dystrophy, recessive Benign:1
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Miyoshi myopathy Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at