rs104894689
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_024301.5(FKRP):c.764G>A(p.Trp255Ter) variant causes a stop gained change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
FKRP
NM_024301.5 stop_gained
NM_024301.5 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 5.97
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 Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 206 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 19-46756214-G-A is Pathogenic according to our data. Variant chr19-46756214-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 4230.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-46756214-G-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FKRP | NM_024301.5 | c.764G>A | p.Trp255Ter | stop_gained | 4/4 | ENST00000318584.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FKRP | ENST00000318584.10 | c.764G>A | p.Trp255Ter | stop_gained | 4/4 | 1 | NM_024301.5 | P1 | |
FKRP | ENST00000391909.7 | c.764G>A | p.Trp255Ter | stop_gained | 4/4 | 2 | P1 | ||
FKRP | ENST00000597339.5 | n.247-5619G>A | intron_variant, non_coding_transcript_variant | 5 | |||||
FKRP | ENST00000600646.5 | n.247+7549G>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1295864Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 636532
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1295864
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
636532
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2I Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2003 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A;A
Vest4
GERP RS
Splicing
Name
Calibrated prediction
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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