Variant 14-21031026-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173846.5(TPPP2):c.188G>A(p.Arg63Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000733 in 1,610,044 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

TPPP2
NM_173846.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.63

Variant links:

Genes affected

TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TPPP2 links:

TPPP2 (HGNC:):

TPPP2 links:

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

NDRG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1419782).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP2	NM_173846.5 linkuse as main transcript	c.188G>A	p.Arg63Gln	missense_variant	3/4	ENST00000321760.11	NP_776245.2	P59282

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TPPP2	ENST00000321760.11 linkuse as main transcript	c.188G>A	p.Arg63Gln	missense_variant	3/4	1	NM_173846.5	ENSP00000317595.6		P59282

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152194

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:

0.000385

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000688

AC:

AN:

247244

Hom.:

AF XY:

0.0000823

AC XY:

AN XY:

133584

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000595

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.000236

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000445

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000748

AC:

109

AN:

1457732

Hom.:

Cov.:

AF XY:

0.0000897

AC XY:

AN XY:

724960

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000479

Gnomad4 SAS exome

AF:

0.000199

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000576

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.0000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 30, 2023

The c.188G>A (p.R63Q) alteration is located in exon 3 (coding exon 2) of the TPPP2 gene. This alteration results from a G to A substitution at nucleotide position 188, causing the arginine (R) at amino acid position 63 to be replaced by a glutamine (Q). 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

Pathogenic

0.62

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.12

T;.;T;.;T

Eigen

Benign

0.069

Eigen_PC

Benign

0.12

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.14

T;T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.6

M;.;M;.;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-3.0

D;D;D;D;D

REVEL

Benign

0.19

Sift

Benign

0.046

D;D;D;D;D

Sift4G

Benign

0.065

T;T;T;T;T

Polyphen

0.080

B;.;B;.;.

Vest4

0.80

MVP

0.099

MPC

0.28

ClinPred

0.46

GERP RS

4.0

Varity_R

0.26

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: 20

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