Variant 15-77998288-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_144572.2(TBC1D2B):c.2764G>A(p.Ala922Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00268 in 1,605,042 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 4 hom. )

Consequence

TBC1D2B
NM_144572.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.598

Variant links:

Genes affected

TBC1D2B (HGNC:29183): (TBC1 domain family member 2B) Predicted to enable GTPase activator activity. Predicted to be involved in activation of GTPase activity and intracellular protein transport. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TBC1D2B links:

TBC1D2B (HGNC:):

TBC1D2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004140377).

BP6

Variant 15-77998288-C-T is Benign according to our data. Variant chr15-77998288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3388163.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00179 (273/152290) while in subpopulation SAS AF= 0.0029 (14/4820). AF 95% confidence interval is 0.00226. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TBC1D2B	NM_144572.2 linkuse as main transcript	c.2764G>A	p.Ala922Thr	missense_variant	13/13	ENST00000300584.8	NP_653173.1	Q9UPU7-1B2RTQ2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TBC1D2B	ENST00000300584.8 linkuse as main transcript	c.2764G>A	p.Ala922Thr	missense_variant	13/13	5	NM_144572.2	ENSP00000300584.3		Q9UPU7-1

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

273

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000628

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000981

Gnomad ASJ

AF:

0.0104

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00257

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00203

AC:

477

AN:

235352

Hom.:

AF XY:

0.00211

AC XY:

269

AN XY:

127362

show subpopulations

Gnomad AFR exome

AF:

0.000763

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00884

Gnomad EAS exome

AF:

0.0000583

Gnomad SAS exome

AF:

0.00152

Gnomad FIN exome

AF:

0.000145

Gnomad NFE exome

AF:

0.00261

Gnomad OTH exome

AF:

0.00206

GnomAD4 exome

AF:

0.00277

AC:

4023

AN:

1452752

Hom.:

Cov.:

AF XY:

0.00279

AC XY:

2016

AN XY:

721692

show subpopulations

Gnomad4 AFR exome

AF:

0.000510

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00963

Gnomad4 EAS exome

AF:

0.0000510

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.000285

Gnomad4 NFE exome

AF:

0.00305

Gnomad4 OTH exome

AF:

0.00266

GnomAD4 genome

AF:

0.00179

AC:

273

AN:

152290

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.000626

Gnomad4 AMR

AF:

0.000980

Gnomad4 ASJ

AF:

0.0104

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00257

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00296

Hom.:

Bravo

AF:

0.00182

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00171

AC:

207

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

TBC1D2B: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.4

DANN

Benign

0.92

DEOGEN2

Benign

0.0065

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.82

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.68

REVEL

Benign

0.013

Sift

Benign

0.42

Sift4G

Benign

0.58

Polyphen

0.031

Vest4

0.040

MVP

0.030

MPC

0.26

ClinPred

0.0055

GERP RS

-3.3

Varity_R

0.020

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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