rs78781527

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001102401.4(TTI2):c.118C>T(p.Pro40Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00708 in 1,614,082 control chromosomes in the GnomAD database, including 61 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 1 hom., cov: 31)

Exomes 𝑓: 0.0073 ( 60 hom. )

Consequence

TTI2
NM_001102401.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.628

Variant links:

Genes affected

TTI2 (HGNC:26262): (TELO2 interacting protein 2) This gene encodes a regulator of the DNA damage response. The protein is a component of the Triple T complex (TTT) which also includes telomere length regulation protein and TELO2 interacting protein 1. The TTT complex is involved in cellular resistance to DNA damage stresses and may act as a regulator of phosphoinositide-3-kinase-related protein kinase (PIKK) abundance. [provided by RefSeq, May 2013]

TTI2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038638413).

BP6

Variant 8-33512496-G-A is Benign according to our data. Variant chr8-33512496-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 437085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00499 (759/152200) while in subpopulation NFE AF= 0.00833 (567/68032). AF 95% confidence interval is 0.00777. There are 1 homozygotes in gnomad4. There are 325 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTI2	NM_001102401.4 link	c.118C>T	p.Pro40Ser	missense_variant	Exon 2 of 8	ENST00000431156.7	NP_001095871.1	Q6NXR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTI2	ENST00000431156.7 link	c.118C>T	p.Pro40Ser	missense_variant	Exon 2 of 8	1	NM_001102401.4	ENSP00000411169.3		Q6NXR4

Frequencies

GnomAD3 genomes

AF:

0.00498

AC:

758

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00832

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00472

AC:

1187

AN:

251382

Hom.:

AF XY:

0.00480

AC XY:

652

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00595

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.00240

Gnomad NFE exome

AF:

0.00773

Gnomad OTH exome

AF:

0.00505

GnomAD4 exome

AF:

0.00730

AC:

10668

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5192

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00128

Gnomad4 AMR exome

AF:

0.00331

Gnomad4 ASJ exome

AF:

0.00597

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00129

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.00871

Gnomad4 OTH exome

AF:

0.00628

GnomAD4 genome

AF:

0.00499

AC:

759

AN:

152200

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

325

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00833

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00702

Hom.:

Bravo

AF:

0.00522

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00498

AC:

605

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00725

EpiControl

AF:

0.00717

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TTI2: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Dec 16, 2016

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.0078

T;T;T;.;T

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.74

T;.;.;T;T

MetaRNN

Benign

0.0039

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L;L;.;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.38

.;N;N;N;D

REVEL

Benign

0.063

Sift

Benign

0.34

.;T;T;T;T

Sift4G

Benign

0.18

T;T;T;T;T

Polyphen

0.035

B;B;B;B;.

Vest4

0.076

MVP

0.33

MPC

0.15

ClinPred

0.0094

GERP RS

4.4

Varity_R

0.050

gMVP

0.079

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over