rs72827543
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001130987.2(DYSF):c.2110-43G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0195 in 1,490,578 control chromosomes in the GnomAD database, including 348 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.017 ( 33 hom., cov: 33)
Exomes 𝑓: 0.020 ( 315 hom. )
Consequence
DYSF
NM_001130987.2 intron
NM_001130987.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.24
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=-0.65).
BP6
?
Variant 2-71555922-G-T is Benign according to our data. Variant chr2-71555922-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 259070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-71555922-G-T is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0171 (2607/152326) while in subpopulation NFE AF= 0.0254 (1727/68008). AF 95% confidence interval is 0.0244. There are 33 homozygotes in gnomad4. There are 1285 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 33 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.2110-43G>T | intron_variant | ENST00000410020.8 | |||
DYSF | NM_003494.4 | c.2056-43G>T | intron_variant | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000258104.8 | c.2056-43G>T | intron_variant | 1 | NM_003494.4 | A1 | |||
DYSF | ENST00000410020.8 | c.2110-43G>T | intron_variant | 1 | NM_001130987.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0171 AC: 2607AN: 152208Hom.: 33 Cov.: 33
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GnomAD3 exomes AF: 0.0135 AC: 2093AN: 154846Hom.: 27 AF XY: 0.0131 AC XY: 1070AN XY: 81692
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GnomAD4 exome AF: 0.0198 AC: 26474AN: 1338252Hom.: 315 Cov.: 22 AF XY: 0.0191 AC XY: 12686AN XY: 663458
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GnomAD4 genome ? AF: 0.0171 AC: 2607AN: 152326Hom.: 33 Cov.: 33 AF XY: 0.0173 AC XY: 1285AN XY: 74484
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
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 19, 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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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at