rs142483266
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001130987.2(DYSF):āc.4629C>Gā(p.Val1543=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,613,974 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001130987.2 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.4629C>G | p.Val1543= | splice_region_variant, synonymous_variant | 43/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.4512C>G | p.Val1504= | splice_region_variant, synonymous_variant | 42/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.4629C>G | p.Val1543= | splice_region_variant, synonymous_variant | 43/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.4512C>G | p.Val1504= | splice_region_variant, synonymous_variant | 42/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00105 AC: 160AN: 152130Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000815 AC: 205AN: 251476Hom.: 0 AF XY: 0.000853 AC XY: 116AN XY: 135912
GnomAD4 exome AF: 0.00164 AC: 2402AN: 1461844Hom.: 6 Cov.: 31 AF XY: 0.00154 AC XY: 1119AN XY: 727228
GnomAD4 genome ? AF: 0.00105 AC: 160AN: 152130Hom.: 1 Cov.: 32 AF XY: 0.000982 AC XY: 73AN XY: 74322
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 28, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 17, 2015 | - - |
Qualitative or quantitative defects of dysferlin Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2B Benign:1
Likely benign, no assertion criteria provided | clinical testing | Natera, Inc. | Nov 11, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at