Variant 9-98199422-C-T 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_001267571.2(TBC1D2):c.2746G>A(p.Glu916Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00699 in 1,613,802 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0060 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0071 ( 44 hom. )

Consequence

TBC1D2
NM_001267571.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.450

Variant links:

Genes affected

TBC1D2 (HGNC:18026): (TBC1 domain family member 2) Enables GTPase activator activity and cadherin binding activity. Involved in positive regulation of GTPase activity. Located in several cellular components, including cytoplasmic vesicle; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D2 links:

TBC1D2 (HGNC:):

TBC1D2 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=0.003650248).

BP6

Variant 9-98199422-C-T is Benign according to our data. Variant chr9-98199422-C-T is described in ClinVar as [Benign]. Clinvar id is 770388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2	NM_001267571.2 linkuse as main transcript	c.2746G>A	p.Glu916Lys	missense_variant	13/13	ENST00000465784.7	NP_001254500.1	Q9BYX2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D2	ENST00000465784.7 linkuse as main transcript	c.2746G>A	p.Glu916Lys	missense_variant	13/13	1	NM_001267571.2	ENSP00000481721.1		Q9BYX2-1

Frequencies

GnomAD3 genomes

AF:

0.00597

AC:

909

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00179

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00392

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.00565

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00813

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00755

AC:

1894

AN:

250816

Hom.:

AF XY:

0.00823

AC XY:

1117

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.00204

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0120

Gnomad FIN exome

AF:

0.00758

Gnomad NFE exome

AF:

0.00850

Gnomad OTH exome

AF:

0.00751

GnomAD4 exome

AF:

0.00710

AC:

10379

AN:

1461510

Hom.:

Cov.:

AF XY:

0.00741

AC XY:

5384

AN XY:

727068

show subpopulations

Gnomad4 AFR exome

AF:

0.00125

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0119

Gnomad4 FIN exome

AF:

0.00714

Gnomad4 NFE exome

AF:

0.00695

Gnomad4 OTH exome

AF:

0.00734

GnomAD4 genome

AF:

0.00596

AC:

908

AN:

152292

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.00392

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.00565

Gnomad4 NFE

AF:

0.00813

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00824

Hom.:

Bravo

AF:

0.00527

TwinsUK

AF:

0.00944

AC:

ALSPAC

AF:

0.00649

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00930

AC:

ExAC

AF:

0.00773

AC:

938

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00938

EpiControl

AF:

0.00901

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0067

T;.;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.60

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

T;T;T;T

MetaRNN

Benign

0.0037

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.3

M;.;.;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.3

.;N;N;N

REVEL

Benign

0.028

Sift

Uncertain

0.016

.;D;D;D

Sift4G

Benign

0.14

T;T;T;T

Polyphen

0.31

B;.;.;B

Vest4

0.092

MVP

0.37

MPC

0.34

ClinPred

0.012

GERP RS

3.5

Varity_R

0.048

gMVP

0.31

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