rs1555739333
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PM4PP5_Moderate
The NM_024301.5(FKRP):c.1475del(p.Thr492ArgfsTer28) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
FKRP
NM_024301.5 frameshift
NM_024301.5 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.918
Genes affected
FKRP (HGNC:17997): (fukutin related protein) This gene encodes a protein which is targeted to the medial Golgi apparatus and is necessary for posttranslational modification of dystroglycan. Mutations in this gene have been associated with congenital muscular dystrophy, cognitive disability, and cerebellar cysts. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been determined. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 593 codons.
PP5
?
Variant 19-46756924-AC-A is Pathogenic according to our data. Variant chr19-46756924-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 556566.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-46756924-AC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.1475del | p.Thr492ArgfsTer28 | frameshift_variant | 4/4 | ENST00000318584.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKRP | ENST00000318584.10 | c.1475del | p.Thr492ArgfsTer28 | frameshift_variant | 4/4 | 1 | NM_024301.5 | P1 | |
FKRP | ENST00000391909.7 | c.1475del | p.Thr492ArgfsTer28 | frameshift_variant | 4/4 | 2 | P1 | ||
FKRP | ENST00000597339.5 | n.247-4908del | intron_variant, non_coding_transcript_variant | 5 | |||||
FKRP | ENST00000600646.5 | n.247+8260del | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 2I Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Feb 07, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at