Variant 10-133282347-G-A 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>T 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 0.000917 in 1,584,424 control chromosomes in the GnomAD database, including 2 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 0.00063 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 2 hom. )

Consequence

TUBGCP2
NM_006659.4 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00003168

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-A is Benign according to our data. Variant chr10-133282347-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025110.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>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	ENST00000252936.8
TUBGCP2	NM_001256617.2 linkuse as main transcript	c.2374-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TUBGCP2	NM_001256618.2 linkuse as main transcript	c.1900-5C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant
TUBGCP2	NR_046330.2 linkuse as main transcript	n.3010-5C>T	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>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_006659.4	P1	Q9BSJ2-1

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.000926

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000577

AC:

132

AN:

228596

Hom.:

AF XY:

0.000601

AC XY:

AN XY:

124732

show subpopulations

Gnomad AFR exome

AF:

0.000135

Gnomad AMR exome

AF:

0.000751

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000188

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000942

Gnomad OTH exome

AF:

0.000540

GnomAD4 exome

AF:

0.000948

AC:

1357

AN:

1432114

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

647

AN XY:

708838

show subpopulations

Gnomad4 AFR exome

AF:

0.0000621

Gnomad4 AMR exome

AF:

0.000757

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000145

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00114

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000630

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.000680

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

Jul 28, 2022

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

Feb 01, 2024

TUBGCP2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

1.3

Dann

Benign

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000032

dbscSNV1_RF

Benign

0.0

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