rs149875093
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_001130987.2(DYSF):c.1033+43del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0458 in 1,612,022 control chromosomes in the GnomAD database, including 1,994 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.036 ( 124 hom., cov: 32)
Exomes 𝑓: 0.047 ( 1870 hom. )
Consequence
DYSF
NM_001130987.2 intron
NM_001130987.2 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.204
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 -16 ACMG points.
BP6
Variant 2-71520250-CT-C is Benign according to our data. Variant chr2-71520250-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 259088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71520250-CT-C is described in Lovd as [Benign].
BA1
GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.1033+43del | intron_variant | ENST00000410020.8 | |||
DYSF | NM_003494.4 | c.937+43del | intron_variant | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000258104.8 | c.937+43del | intron_variant | 1 | NM_003494.4 | A1 | |||
DYSF | ENST00000410020.8 | c.1033+43del | intron_variant | 1 | NM_001130987.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0362 AC: 5516AN: 152172Hom.: 124 Cov.: 32
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GnomAD3 exomes AF: 0.0349 AC: 8774AN: 251478Hom.: 188 AF XY: 0.0359 AC XY: 4882AN XY: 135914
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GnomAD4 exome AF: 0.0468 AC: 68387AN: 1459734Hom.: 1870 Cov.: 32 AF XY: 0.0464 AC XY: 33679AN XY: 726390
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GnomAD4 genome AF: 0.0363 AC: 5522AN: 152288Hom.: 124 Cov.: 32 AF XY: 0.0342 AC XY: 2544AN XY: 74448
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 14, 2018 | 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. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at