Variant 10-133282347-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_006659.4(TUBGCP2):c.2290-5C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000819 in 1,584,422 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00066 ( 3 hom. )

Consequence

TUBGCP2
NM_006659.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001002

Clinical Significance

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

Conservation

PhyloP100: 0.500

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-133282347-G-T is Benign according to our data. Variant chr10-133282347-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1694574.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
TUBGCP2	NM_006659.4 linkuse as main transcript	c.2290-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000252936.8
TUBGCP2	NM_001256617.2 linkuse as main transcript	c.2374-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TUBGCP2	NM_001256618.2 linkuse as main transcript	c.1900-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TUBGCP2	NR_046330.2 linkuse as main transcript	n.3010-5C>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TUBGCP2	ENST00000252936.8 linkuse as main transcript	c.2290-5C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_006659.4	P1	Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.00232

AC:

353

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00642

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000808

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000923

AC:

211

AN:

228596

Hom.:

AF XY:

0.000802

AC XY:

100

AN XY:

124732

show subpopulations

Gnomad AFR exome

AF:

0.00650

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000593

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000387

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.000540

GnomAD4 exome

AF:

0.000659

AC:

944

AN:

1432112

Hom.:

Cov.:

AF XY:

0.000640

AC XY:

454

AN XY:

708838

show subpopulations

Gnomad4 AFR exome

AF:

0.00637

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.0000797

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000730

Gnomad4 NFE exome

AF:

0.000535

Gnomad4 OTH exome

AF:

0.000964

GnomAD4 genome

AF:

0.00232

AC:

354

AN:

152310

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

159

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00642

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.000809

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000432

Hom.:

Bravo

AF:

0.00282

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

TUBGCP2-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 29, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

TUBGCP2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

3.1

Dann

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0010

dbscSNV1_RF

Benign

0.14

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