rs1553376558
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001130987.2(DYSF):c.3827del(p.Phe1276SerfsTer3) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
DYSF
NM_001130987.2 frameshift
NM_001130987.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.45
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 Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-71600770-GT-G is Pathogenic according to our data. Variant chr2-71600770-GT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 553990.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-71600770-GT-G is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DYSF | NM_001130987.2 | c.3827del | p.Phe1276SerfsTer3 | frameshift_variant | 34/56 | ENST00000410020.8 | |
DYSF | NM_003494.4 | c.3773del | p.Phe1258SerfsTer3 | frameshift_variant | 34/55 | ENST00000258104.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DYSF | ENST00000410020.8 | c.3827del | p.Phe1276SerfsTer3 | frameshift_variant | 34/56 | 1 | NM_001130987.2 | A1 | |
DYSF | ENST00000258104.8 | c.3773del | p.Phe1258SerfsTer3 | frameshift_variant | 34/55 | 1 | NM_003494.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461398Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727026
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727026
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2B Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Oct 05, 2017 | - - |
Computational scores
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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