rs373693348

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_006659.4(TUBGCP2):c.2374G>T(p.Ala792Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000385 in 1,611,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A792T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

TUBGCP2
NM_006659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.484

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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03982547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TUBGCP2	NM_006659.4 link	c.2374G>T	p.Ala792Ser	missense_variant	Exon 16 of 18	ENST00000252936.8	NP_006650.1	Q9BSJ2-1Q53EQ3
TUBGCP2	NM_001256617.2 link	c.2458G>T	p.Ala820Ser	missense_variant	Exon 17 of 19		NP_001243546.1	Q9BSJ2-4
TUBGCP2	NM_001256618.2 link	c.1984G>T	p.Ala662Ser	missense_variant	Exon 15 of 17		NP_001243547.1	Q9BSJ2-3
TUBGCP2	NR_046330.2 link	n.3094G>T		non_coding_transcript_exon_variant	Exon 16 of 18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TUBGCP2	ENST00000252936.8 link	c.2374G>T	p.Ala792Ser	missense_variant	Exon 16 of 18	2	NM_006659.4	ENSP00000252936.3		Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000328

AC:

AN:

243866

AF XY:

0.0000301

show subpopulations

Gnomad AFR exome

AF:

0.000393

Gnomad AMR exome

AF:

0.0000585

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000151

AC:

AN:

1459412

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

725984

show subpopulations

African (AFR)

AF:

0.000478

AC:

AN:

33442

American (AMR)

AF:

0.0000897

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.00

AC:

AN:

86040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111286

Other (OTH)

AF:

0.0000332

AC:

AN:

60268

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

GnomAD4 genome

AF:

0.000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.000842

AC:

AN:

41562

American (AMR)

AF:

0.000327

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000230

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 22, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.2374G>T (p.A792S) alteration is located in exon 16 (coding exon 15) of the TUBGCP2 gene. This alteration results from a G to T substitution at nucleotide position 2374, causing the alanine (A) at amino acid position 792 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.056

T;.;.;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.85

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.52

.;T;T;T;T

M_CAP

Benign

0.0081

MetaRNN

Benign

0.040

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

N;.;.;N;.

PhyloP100

0.48

PrimateAI

Benign

0.34

PROVEAN

Benign

0.68

N;N;N;N;N

REVEL

Benign

0.013

Sift

Benign

0.31

T;T;T;T;T

Sift4G

Benign

0.60

T;T;T;T;T

Polyphen

0.0010

B;.;.;B;.

Vest4

0.18

MVP

0.25

MPC

0.26

ClinPred

0.0085

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.021

gMVP

0.094

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

rs373693348

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