rs12470028
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001130987.2(DYSF):c.239+20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0807 in 1,601,178 control chromosomes in the GnomAD database, including 6,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.090 ( 733 hom., cov: 32)
Exomes 𝑓: 0.080 ( 5924 hom. )
Consequence
DYSF
NM_001130987.2 intron
NM_001130987.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0680
Genes affected
DYSF (HGNC:3097): (dysferlin) The protein encoded by this gene belongs to the ferlin family and is a skeletal muscle protein found associated with the sarcolemma. It is involved in muscle contraction and contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. In addition, the protein encoded by this gene binds caveolin-3, a skeletal muscle membrane protein which is important in the formation of caveolae. Specific mutations in this gene have been shown to cause autosomal recessive limb girdle muscular dystrophy type 2B (LGMD2B) as well as Miyoshi myopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BP6
?
Variant 2-71481990-G-A is Benign according to our data. Variant chr2-71481990-G-A is described in ClinVar as [Benign]. Clinvar id is 94288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71481990-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.239+20G>A | intron_variant | ENST00000410020.8 | |||
DYSF | NM_003494.4 | c.236+20G>A | intron_variant | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000258104.8 | c.236+20G>A | intron_variant | 1 | NM_003494.4 | A1 | |||
DYSF | ENST00000410020.8 | c.239+20G>A | intron_variant | 1 | NM_001130987.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0899 AC: 13678AN: 152102Hom.: 734 Cov.: 32
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GnomAD3 exomes AF: 0.0974 AC: 24269AN: 249230Hom.: 1989 AF XY: 0.0911 AC XY: 12266AN XY: 134608
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GnomAD4 exome AF: 0.0797 AC: 115446AN: 1448958Hom.: 5924 Cov.: 27 AF XY: 0.0788 AC XY: 56824AN XY: 721570
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GnomAD4 genome ? AF: 0.0900 AC: 13695AN: 152220Hom.: 733 Cov.: 32 AF XY: 0.0886 AC XY: 6594AN XY: 74434
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 28, 2016 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 24, 2015 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Miyoshi muscular dystrophy 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Qualitative or quantitative defects of dysferlin Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at