Variant chr9-98200284-G-A 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.2548C>T(p.Arg850Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00363 in 1,613,882 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0037 ( 26 hom. )

Consequence

TBC1D2
NM_001267571.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.62

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=0.016935587).

BP6

Variant 9-98200284-G-A is Benign according to our data. Variant chr9-98200284-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710851.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.2548C>T	p.Arg850Cys	missense_variant	12/13	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.2548C>T	p.Arg850Cys	missense_variant	12/13	1	NM_001267571.2	ENSP00000481721.1		Q9BYX2-1

Frequencies

GnomAD3 genomes

AF:

0.00298

AC:

453

AN:

151972

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00407

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00213

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00236

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00337

AC:

847

AN:

251330

Hom.:

AF XY:

0.00329

AC XY:

447

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00252

Gnomad ASJ exome

AF:

0.00397

Gnomad EAS exome

AF:

0.00114

Gnomad SAS exome

AF:

0.00468

Gnomad FIN exome

AF:

0.00231

Gnomad NFE exome

AF:

0.00411

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00370

AC:

5403

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

2679

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00239

Gnomad4 ASJ exome

AF:

0.00375

Gnomad4 EAS exome

AF:

0.000605

Gnomad4 SAS exome

AF:

0.00537

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.00383

Gnomad4 OTH exome

AF:

0.00401

GnomAD4 genome

AF:

0.00298

AC:

453

AN:

152090

Hom.:

Cov.:

AF XY:

0.00281

AC XY:

209

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000723

Gnomad4 AMR

AF:

0.00406

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00213

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00236

Gnomad4 NFE

AF:

0.00409

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00392

Hom.:

Bravo

AF:

0.00274

TwinsUK

AF:

0.00243

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00329

AC:

399

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.00425

EpiControl

AF:

0.00528

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.19

T;.;.;.;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Pathogenic

3.0

M;.;M;.;.

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-6.6

.;D;D;D;D

REVEL

Benign

0.29

Sift

Pathogenic

0.0

.;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0

D;.;.;.;D

Vest4

0.65

MVP

0.63

MPC

1.1

ClinPred

0.10

GERP RS

4.5

Varity_R

0.69

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