2-165940940-C-A

Variant names:

• chr2-165940940-C-A
• rs7592392
• NM_024753.5:c.710+87G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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-AS1 (HGNC:41115): (TTC21B antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	NM_024753.5	MANE Select	c.710+87G>T		intron	N/A	NP_079029.3
	TTC21B-AS1	NR_038983.1		n.276+6151C>A		intron	N/A
	TTC21B-AS1	NR_038984.1		n.221-6257C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTC21B	ENST00000243344.8	TSL:1 MANE Select	c.710+87G>T		intron	N/A	ENSP00000243344.7	Q7Z4L5-1
	TTC21B	ENST00000464374.5	TSL:1	n.750+87G>T		intron	N/A
	TTC21B	ENST00000679840.1		c.710+87G>T		intron	N/A	ENSP00000505248.1	A0A7P0T8P4

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

African (AFR) AF: 0.579 AC: 17330 AN: 29914

American (AMR) AF: 0.771 AC: 32459 AN: 42110

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 14680 AN: 24948

East Asian (EAS) AF: 0.807 AC: 31160 AN: 38636

South Asian (SAS) AF: 0.664 AC: 53683 AN: 80810

European-Finnish (FIN) AF: 0.668 AC: 34785 AN: 52084

Middle Eastern (MID) AF: 0.698 AC: 2985 AN: 4278

European-Non Finnish (NFE) AF: 0.608 AC: 597857 AN: 982724

Other (OTH) AF: 0.622 AC: 34243 AN: 55052

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

African (AFR) AF: 0.575 AC: 23810 AN: 41438

American (AMR) AF: 0.714 AC: 10896 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2034 AN: 3462

East Asian (EAS) AF: 0.807 AC: 4171 AN: 5170

South Asian (SAS) AF: 0.674 AC: 3252 AN: 4824

European-Finnish (FIN) AF: 0.665 AC: 7014 AN: 10546

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41543 AN: 67930

Other (OTH) AF: 0.634 AC: 1340 AN: 2114

Alfa AF: 0.543 Hom.: 2231

Bravo AF: 0.628

Asia WGS AF: 0.706 AC: 2457 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.61
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7592392; hg19: chr2-166797450;