chr2-165953686-T-TCACCCGCTCACCCGC

Position:

• chr2-165953686-T-TCACCCGCTCACCCGC

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The ENST00000243344.8(TTC21B):​c.19_20insGCGGGTGAGCGGGTG​(p.Lys7delinsSerGlyTer) variant causes a stop gained, protein altering, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000177 in 56,570 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: 𝑓 0.000018 (0 hom., cov: 26)
  • Exomes 𝑓: 0.0000072 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TTC21B ENST00000243344.8 stop_gained, protein_altering, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 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 73 pathogenic variants in the truncated region.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21B	NM_024753.5	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTer	stop_gained, protein_altering_variant, splice_region_variant	1/29	ENST00000243344.8	NP_079029.3
TTC21B	XM_006712761.2	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTer	stop_gained, protein_altering_variant, splice_region_variant	1/23		XP_006712824.1
TTC21B	XM_011511872.3	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTer	stop_gained, protein_altering_variant, splice_region_variant	1/21		XP_011510174.1
TTC21B	XM_017004967.2	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTer	stop_gained, protein_altering_variant, splice_region_variant	1/28		XP_016860456.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.19_20insGCGGGTGAGCGGGTG	p.Lys7delinsSerGlyTer	stop_gained, protein_altering_variant, splice_region_variant	1/29	1	NM_024753.5	ENSP00000243344	P1

Frequencies

GnomAD3 genomes AF: 0.0000177 AC: 1 AN: 56570 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.0000713

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000718 AC: 4 AN: 556982 Hom.: 0 Cov.: 36 AF XY: 0.00 AC XY: 0 AN XY: 279116

Gnomad4 AFR exome AF: 0.000329

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000177 AC: 1 AN: 56570 Hom.: 0 Cov.: 26 AF XY: 0.0000361 AC XY: 1 AN XY: 27698

Gnomad4 AFR AF: 0.0000713

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs759648976; hg19: chr2-166810196;