chr2-165940940-C-A

Position:

• chr2-165940940-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024753.5(TTC21B):​c.710+87G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 1,462,512 control chromosomes in the GnomAD database, including 288,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29856 hom., cov: 32)
  • Exomes 𝑓: 0.63 (258442 hom.)
• Consequence: TTC21B NM_024753.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.952

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-AS1 (HGNC:41115): (TTC21B antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-165940940-C-A is Benign according to our data. Variant chr2-165940940-C-A is described in ClinVar as [Benign]. Clinvar id is 1243445.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTC21B	NM_024753.5	c.710+87G>T		intron_variant		ENST00000243344.8	NP_079029.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTC21B	ENST00000243344.8	c.710+87G>T		intron_variant		1	NM_024753.5	ENSP00000243344.7

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94704 AN: 151838 Hom.: 29829 Cov.: 32

Gnomad AFR AF: 0.574

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.673

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.637

GnomAD4 exome AF: 0.625 AC: 819182 AN: 1310556 Hom.: 258442 AF XY: 0.627 AC XY: 412857 AN XY: 658532

Gnomad4 AFR exome AF: 0.579

Gnomad4 AMR exome AF: 0.771

Gnomad4 ASJ exome AF: 0.588

Gnomad4 EAS exome AF: 0.807

Gnomad4 SAS exome AF: 0.664

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.608

Gnomad4 OTH exome AF: 0.622

GnomAD4 genome AF: 0.624 AC: 94786 AN: 151956 Hom.: 29856 Cov.: 32 AF XY: 0.630 AC XY: 46756 AN XY: 74266

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.807

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.612

Gnomad4 OTH AF: 0.634

Alfa AF: 0.543 Hom.: 2231

Bravo AF: 0.628

Asia WGS AF: 0.706 AC: 2457 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.61

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: rs7592392; hg19: chr2-166797450;