rs138371601

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_ModerateBS1

The NM_144572.2(TBC1D2B):c.2326G>A(p.Val776Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,608,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

TBC1D2B
NM_144572.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.64

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with seizures and gingival overgrowth
Inheritance: AR Classification: STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

TBC1D2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14477512).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0000394 (6/152230) while in subpopulation AFR AF = 0.00012 (5/41542). AF 95% confidence interval is 0.0000473. There are 0 homozygotes in GnomAd4. There are 2 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144572.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D2B	NM_144572.2	MANE Select	c.2326G>A	p.Val776Ile	missense	Exon 10 of 13	NP_653173.1	Q9UPU7-1
TBC1D2B	NM_001387142.1		c.2326G>A	p.Val776Ile	missense	Exon 10 of 14	NP_001374071.1
TBC1D2B	NM_001387143.1		c.2323G>A	p.Val775Ile	missense	Exon 10 of 13	NP_001374072.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TBC1D2B	ENST00000300584.8	TSL:5 MANE Select	c.2326G>A	p.Val776Ile	missense	Exon 10 of 13	ENSP00000300584.3	Q9UPU7-1
TBC1D2B	ENST00000409931.7	TSL:1	c.2326G>A	p.Val776Ile	missense	Exon 10 of 13	ENSP00000387165.3	Q9UPU7-2
TBC1D2B	ENST00000936499.1		c.2326G>A	p.Val776Ile	missense	Exon 10 of 13	ENSP00000606558.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000247

AC:

AN:

242536

AF XY:

0.00000765

show subpopulations

Gnomad AFR exome

AF:

0.000260

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1456740

Hom.:

Cov.:

AF XY:

0.00000967

AC XY:

AN XY:

723938

show subpopulations

African (AFR)

AF:

0.0000898

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44088

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84922

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1109548

Other (OTH)

AF:

0.0000332

AC:

AN:

60238

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.430

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41542

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000262

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000911

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

Eigen

Benign

0.10

Eigen_PC

Benign

0.14

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0066

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.9

PhyloP100

2.6

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.79

REVEL

Benign

0.079

Sift

Benign

0.033

Sift4G

Uncertain

0.018

Polyphen

0.54

Vest4

0.19

MVP

0.51

MPC

0.32

ClinPred

0.52

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.17

gMVP

0.31

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over