chr2-165953686-T-TCACCC
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_024753.5(TTC21B):c.19_20insGGGTG(p.Lys7ArgfsTer5) variant causes a frameshift, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000898 in 557,028 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 26)
Exomes 𝑓: 0.0000090 ( 0 hom. )
Consequence
TTC21B
NM_024753.5 frameshift, splice_region
NM_024753.5 frameshift, splice_region
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.359
Publications
0 publications found
Genes affected
TTC21B (HGNC:25660): (tetratricopeptide repeat domain 21B) This gene encodes a member of TTC21 family, containing several tetratricopeptide repeat (TPR) domains. This protein is localized to the cilium axoneme, and may play a role in retrograde intraflagellar transport in cilia. Mutations in this gene are associated with various ciliopathies, nephronophthisis 12, and asphyxiating thoracic dystrophy 4. [provided by RefSeq, Oct 2011]
TTC21B Gene-Disease associations (from GenCC):
- nephronophthisis 12Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
- asphyxiating thoracic dystrophy 4Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
- Jeune syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- nephronophthisis 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 105 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTC21B | NM_024753.5 | c.19_20insGGGTG | p.Lys7ArgfsTer5 | frameshift_variant, splice_region_variant | Exon 1 of 29 | ENST00000243344.8 | NP_079029.3 | |
TTC21B | XM_017004967.2 | c.19_20insGGGTG | p.Lys7ArgfsTer5 | frameshift_variant, splice_region_variant | Exon 1 of 28 | XP_016860456.1 | ||
TTC21B | XM_006712761.2 | c.19_20insGGGTG | p.Lys7ArgfsTer5 | frameshift_variant, splice_region_variant | Exon 1 of 23 | XP_006712824.1 | ||
TTC21B | XM_011511872.3 | c.19_20insGGGTG | p.Lys7ArgfsTer5 | frameshift_variant, splice_region_variant | Exon 1 of 21 | XP_011510174.1 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 26
GnomAD3 genomes
Cov.:
26
GnomAD2 exomes AF: 0.00 AC: 0AN: 54534 AF XY: 0.00
GnomAD2 exomes
AF:
AC:
0
AN:
54534
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000898 AC: 5AN: 557028Hom.: 0 Cov.: 36 AF XY: 0.0000107 AC XY: 3AN XY: 279136 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
557028
Hom.:
Cov.:
36
AF XY:
AC XY:
3
AN XY:
279136
show subpopulations
African (AFR)
AF:
AC:
0
AN:
12208
American (AMR)
AF:
AC:
0
AN:
11324
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
10652
East Asian (EAS)
AF:
AC:
0
AN:
21502
South Asian (SAS)
AF:
AC:
0
AN:
39616
European-Finnish (FIN)
AF:
AC:
0
AN:
25112
Middle Eastern (MID)
AF:
AC:
0
AN:
2740
European-Non Finnish (NFE)
AF:
AC:
5
AN:
408310
Other (OTH)
AF:
AC:
0
AN:
25564
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome Cov.: 26
GnomAD4 genome
Cov.:
26
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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