Variant chr14-21032059-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_173846.5(TPPP2):c.495C>G(p.Tyr165*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00497 in 1,613,678 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 136 hom. )

Consequence

TPPP2
NM_173846.5 stop_gained

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.220

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 Benign. Variant got -16 ACMG points.

BP6

Variant 14-21032059-C-G is Benign according to our data. Variant chr14-21032059-C-G is described in ClinVar as [Benign]. Clinvar id is 776817.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TPPP2	NM_173846.5 linkuse as main transcript	c.495C>G	p.Tyr165*	stop_gained	4/4	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.495C>G	p.Tyr165*	stop_gained	4/4	1	NM_173846.5	ENSP00000317595.6		P59282

Frequencies

GnomAD3 genomes

AF:

0.0228

AC:

3467

AN:

152098

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0759

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00944

Gnomad ASJ

AF:

0.0276

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.00724

AC:

1817

AN:

251076

Hom.:

AF XY:

0.00579

AC XY:

785

AN XY:

135682

show subpopulations

Gnomad AFR exome

AF:

0.0764

Gnomad AMR exome

AF:

0.00448

Gnomad ASJ exome

AF:

0.0307

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000608

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.00310

AC:

4534

AN:

1461462

Hom.:

136

Cov.:

AF XY:

0.00282

AC XY:

2051

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.0796

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.0299

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000299

Gnomad4 OTH exome

AF:

0.00772

GnomAD4 genome

AF:

0.0229

AC:

3482

AN:

152216

Hom.:

115

Cov.:

AF XY:

0.0221

AC XY:

1647

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0761

Gnomad4 AMR

AF:

0.00943

Gnomad4 ASJ

AF:

0.0276

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.0257

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0756

AC:

333

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.00795

AC:

965

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00109

EpiControl

AF:

0.000948

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Pathogenic

0.59

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.34

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.82

Vest4

0.26

GERP RS

3.6

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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