dbSNP rs766195152: TUBGCP2:p.Asn862Ser (chr10-133279890-T-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_006659.4(TUBGCP2):c.2585A>G(p.Asn862Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000168 in 1,609,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

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

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

TUBGCP2
NM_006659.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.84

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):

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.874

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006659.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBGCP2	NM_006659.4	MANE Select	c.2585A>G	p.Asn862Ser	missense	Exon 18 of 18	NP_006650.1	Q9BSJ2-1
TUBGCP2	NM_001256617.2		c.2669A>G	p.Asn890Ser	missense	Exon 19 of 19	NP_001243546.1	Q9BSJ2-4
TUBGCP2	NM_001256618.2		c.2195A>G	p.Asn732Ser	missense	Exon 17 of 17	NP_001243547.1	Q9BSJ2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TUBGCP2	ENST00000252936.8	TSL:2 MANE Select	c.2585A>G	p.Asn862Ser	missense	Exon 18 of 18	ENSP00000252936.3	Q9BSJ2-1
TUBGCP2	ENST00000543663.6	TSL:1	c.2669A>G	p.Asn890Ser	missense	Exon 19 of 19	ENSP00000446093.1	Q9BSJ2-4
TUBGCP2	ENST00000682161.1		c.2654A>G	p.Asn885Ser	missense	Exon 17 of 17	ENSP00000507509.1	A0A804HJH7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000206

AC:

AN:

242866

AF XY:

0.0000303

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000144

AC:

AN:

1457388

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

724890

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33316

American (AMR)

AF:

0.00

AC:

AN:

44154

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39480

South Asian (SAS)

AF:

0.00

AC:

AN:

85686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1110524

Other (OTH)

AF:

0.0000332

AC:

AN:

60240

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

152128

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74310

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.0000654

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68002

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

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:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

0.00067

BayesDel_noAF

Benign

-0.24

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

Eigen

Pathogenic

0.69

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.084

MetaRNN

Pathogenic

0.87

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.8

PhyloP100

4.8

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-4.1

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.81

MutPred

0.72

Loss of catalytic residue at N862 (P = 0.0058)

MVP

0.74

MPC

0.87

ClinPred

0.96

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.60

gMVP

0.74

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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