Variant rs186443359 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001102401.4(TTI2):c.581G>C(p.Gly194Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000481 in 1,614,148 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00046 ( 7 hom. )

Consequence

TTI2
NM_001102401.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.07

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0068973005).

BP6

Variant 8-33512033-C-G is Benign according to our data. Variant chr8-33512033-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 445746.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTI2	NM_001102401.4 linkuse as main transcript	c.581G>C	p.Gly194Ala	missense_variant	2/8	ENST00000431156.7	NP_001095871.1	Q6NXR4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTI2	ENST00000431156.7 linkuse as main transcript	c.581G>C	p.Gly194Ala	missense_variant	2/8	1	NM_001102401.4	ENSP00000411169.3	Q6NXR4
TTI2	ENST00000613904.1 linkuse as main transcript	c.581G>C	p.Gly194Ala	missense_variant	2/8	1		ENSP00000478396.1	Q6NXR4
TTI2	ENST00000360742.9 linkuse as main transcript	c.581G>C	p.Gly194Ala	missense_variant	1/7	2		ENSP00000353971.5	Q6NXR4
TTI2	ENST00000520636.5 linkuse as main transcript	c.581G>C	p.Gly194Ala	missense_variant	1/6	5		ENSP00000428401.1	E5RIH5

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00198

AC:

499

AN:

251488

Hom.:

AF XY:

0.00138

AC XY:

187

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0138

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00293

GnomAD4 exome

AF:

0.000459

AC:

671

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000367

AC XY:

267

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.0141

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:

0.00000629

Gnomad4 OTH exome

AF:

0.000513

GnomAD4 genome

AF:

0.000690

AC:

105

AN:

152266

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.0000908

Hom.:

Bravo

AF:

0.00142

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00164

AC:

199

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 12, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

T;T;T;.

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.87

D;.;.;D

MetaRNN

Benign

0.0069

T;T;T;T

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.8

M;M;M;.

PrimateAI

Benign

0.40

PROVEAN

Benign

-2.3

.;N;N;N

REVEL

Uncertain

0.48

Sift

Benign

0.053

.;T;T;T

Sift4G

Uncertain

0.024

D;D;D;D

Polyphen

1.0

D;D;D;D

Vest4

0.68

MVP

0.67

MPC

0.65

ClinPred

0.041

GERP RS

4.7

Varity_R

0.15

gMVP

0.62

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