Variant 14-21031143-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173846.5(TPPP2):c.305A>G(p.Asp102Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,613,862 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 1 hom. )

Consequence

TPPP2
NM_173846.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037323385).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP2	NM_173846.5 linkuse as main transcript	c.305A>G	p.Asp102Gly	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.305A>G	p.Asp102Gly	missense_variant	3/4	1	NM_173846.5	ENSP00000317595.6		P59282

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152104

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:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000799

AC:

AN:

250178

Hom.:

AF XY:

0.0000591

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00104

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

727114

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00128

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.0000988

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 23, 2023

The c.305A>G (p.D102G) alteration is located in exon 3 (coding exon 2) of the TPPP2 gene. This alteration results from a A to G substitution at nucleotide position 305, causing the aspartic acid (D) at amino acid position 102 to be replaced by a glycine (G). 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

0.12

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0025

T;.;T;.;T

Eigen

Benign

-0.083

Eigen_PC

Benign

0.074

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.80

.;T;T;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.037

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.72

N;N;N;N;N

REVEL

Benign

0.066

Sift

Benign

0.42

T;T;T;T;T

Sift4G

Benign

0.61

T;T;T;T;T

Polyphen

0.18

B;.;B;.;.

Vest4

0.29

MutPred

0.38

Loss of solvent accessibility (P = 0.0595);Loss of solvent accessibility (P = 0.0595);Loss of solvent accessibility (P = 0.0595);Loss of solvent accessibility (P = 0.0595);.;

MVP

0.048

MPC

0.072

ClinPred

0.12

GERP RS

3.6

Varity_R

0.17

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

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