10-133281331-G-A

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006659.4(TUBGCP2):c.2515C>T(p.Arg839Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,384 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

TUBGCP2
NM_006659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 3.08

Publications

1 publications found

Variant links:

Genes affected

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 Gene-Disease associations (from GenCC):

Norman-Roberts syndrome
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

TUBGCP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP2	NM_006659.4 link	c.2515C>T	p.Arg839Trp	missense_variant	Exon 17 of 18	ENST00000252936.8	NP_006650.1	Q9BSJ2-1Q53EQ3
TUBGCP2	NM_001256617.2 link	c.2599C>T	p.Arg867Trp	missense_variant	Exon 18 of 19		NP_001243546.1	Q9BSJ2-4
TUBGCP2	NM_001256618.2 link	c.2125C>T	p.Arg709Trp	missense_variant	Exon 16 of 17		NP_001243547.1	Q9BSJ2-3
TUBGCP2	NR_046330.2 link	n.3235C>T		non_coding_transcript_exon_variant	Exon 17 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP2	ENST00000252936.8 link	c.2515C>T	p.Arg839Trp	missense_variant	Exon 17 of 18	2	NM_006659.4	ENSP00000252936.3		Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000678

AC:

AN:

250892

AF XY:

0.0000663

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000390

AC:

AN:

1461202

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

726926

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

53168

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.0000342

AC:

AN:

1111978

Other (OTH)

AF:

0.0000166

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000577

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 04, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2515C>T (p.R839W) alteration is located in exon 17 (coding exon 16) of the TUBGCP2 gene. This alteration results from a C to T substitution at nucleotide position 2515, causing the arginine (R) at amino acid position 839 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TUBGCP2: PM2:Supporting, BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.31

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.42

T;.;.;T;T

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.97

.;D;D;D;D

M_CAP

Benign

0.024

MetaRNN

Uncertain

0.59

D;D;D;D;D

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.1

M;.;.;M;.

PhyloP100

3.1

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-4.2

D;D;D;D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0030

D;D;D;D;D

Sift4G

Uncertain

0.0040

D;D;D;D;D

Polyphen

0.99

D;.;.;D;.

Vest4

0.55

MutPred

0.56

Gain of catalytic residue at L837 (P = 0.0253);.;.;Gain of catalytic residue at L837 (P = 0.0253);.;

MVP

0.59

MPC

0.91

ClinPred

0.88

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.69

Mutation Taster

=67/33

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

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10-133281331-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over