rs144600502

Positions:

• chr2-165901914-G-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_024753.5(TTC21B):​c.2569-5_2569-4insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00217 in 1,600,870 control chromosomes in the GnomAD database, including 78 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (41 hom.)
• Consequence: TTC21B NM_024753.5 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.346

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 Benign. Variant got -16 ACMG points.

• BP6: Variant 2-165901914-G-GA is Benign according to our data. Variant chr2-165901914-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 195530.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1799/147598) while in subpopulation AFR AF= 0.0427 (1704/39890). AF 95% confidence interval is 0.041. There are 37 homozygotes in gnomad4. There are 824 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TTC21B	NM_024753.5	c.2569-5_2569-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000243344.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TTC21B	ENST00000243344.8	c.2569-5_2569-4insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_024753.5	P1

Frequencies

GnomAD3 genomes AF: 0.0122 AC: 1797 AN: 147484 Hom.: 37 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00515

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00329

Gnomad NFE AF: 0.0000598

Gnomad OTH AF: 0.00691

GnomAD4 exome AF: 0.00115 AC: 1669 AN: 1453272 Hom.: 41 Cov.: 31 AF XY: 0.000975 AC XY: 705 AN XY: 723106

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.00269

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000510

Gnomad4 SAS exome AF: 0.0000703

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000587

Gnomad4 OTH exome AF: 0.00248

GnomAD4 genome AF: 0.0122 AC: 1799 AN: 147598 Hom.: 37 Cov.: 32 AF XY: 0.0115 AC XY: 824 AN XY: 71746

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.00514

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000598

Gnomad4 OTH AF: 0.00684

Alfa AF: 0.00582 Hom.: 1

Bravo AF: 0.0137

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 15, 2014	- -
Likely benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Jeune thoracic dystrophy;C0687120:Nephronophthisis Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2018

- -

Jeune thoracic dystrophy Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Familial aplasia of the vermis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Connective tissue disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs144600502; hg19: chr2-166758424;