rs587777086
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_015662.3(IFT172):βc.2158delβ(p.Arg720ValfsTer28) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000142 in 1,614,062 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β β ). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: π 0.000026 ( 0 hom., cov: 30)
Exomes π: 0.000013 ( 0 hom. )
Consequence
IFT172
NM_015662.3 frameshift
NM_015662.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.33
Genes affected
IFT172 (HGNC:30391): (intraflagellar transport 172) This gene encodes a subunit of the intraflagellar transport subcomplex IFT-B. Subcomplexes IFT-A and IFT-B are necessary for ciliary assembly and maintenance. Mutations in this gene have been associated with skeletal ciliopathies, with or without polydactyly, such as such short-rib thoracic dysplasias 1, 9 or 10. [provided by RefSeq, Mar 2014]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 18 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 2-27461793-CG-C is Pathogenic according to our data. Variant chr2-27461793-CG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 97032.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-27461793-CG-C is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
IFT172 | NM_015662.3 | c.2158del | p.Arg720ValfsTer28 | frameshift_variant | 21/48 | ENST00000260570.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
IFT172 | ENST00000260570.8 | c.2158del | p.Arg720ValfsTer28 | frameshift_variant | 21/48 | 1 | NM_015662.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 30
GnomAD3 genomes
?
AF:
AC:
4
AN:
152178
Hom.:
Cov.:
30
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251346Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135844
GnomAD3 exomes
AF:
AC:
1
AN:
251346
Hom.:
AF XY:
AC XY:
1
AN XY:
135844
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461884Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13AN XY: 727244
GnomAD4 exome
AF:
AC:
19
AN:
1461884
Hom.:
Cov.:
31
AF XY:
AC XY:
13
AN XY:
727244
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152178Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74334
GnomAD4 genome
?
AF:
AC:
4
AN:
152178
Hom.:
Cov.:
30
AF XY:
AC XY:
3
AN XY:
74334
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Pathogenic/Likely pathogenic
Submissions summary: Pathogenic:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Short-rib thoracic dysplasia 10 without polydactyly Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 07, 2013 | - - |
Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | This sequence change creates a premature translational stop signal (p.Arg720Valfs*28) in the IFT172 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT172 are known to be pathogenic (PMID: 24140113). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with short-rib thoracic dysplasia (PMID: 24140113). ClinVar contains an entry for this variant (Variation ID: 97032). For these reasons, this variant has been classified as Pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 06, 2021 | - - |
Short-rib thoracic dysplasia 10 with or without polydactyly;C4225342:Retinitis pigmentosa 71;C4310707:Bardet-Biedl syndrome 20 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Feb 04, 2022 | - - |
Retinitis pigmentosa 71 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | research | Ocular Genomics Institute, Massachusetts Eye and Ear | Apr 08, 2021 | The IFT172 c.2158del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PVS1, PM2. Based on this evidence we have classified this variant as Likely Pathogenic. - |
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