rs2273906

Positions:

chr14-102432026-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014844.5(TECPR2):c.1315C>T(p.Pro439Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0344 in 1,612,818 control chromosomes in the GnomAD database, including 1,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 157 hom., cov: 32)

Exomes 𝑓: 0.034 ( 955 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.911

Variant links:

Genes affected

TECPR2 (HGNC:19957): (tectonin beta-propeller repeat containing 2) The protein encoded by this gene is a member of the tectonin beta-propeller repeat-containing (TECPR) family, and contains both TECPR and tryptophan-aspartic acid repeat (WD repeat) domains. This gene has been implicated in autophagy, as reduced expression levels of this gene have been associated with impaired autophagy. Recessive mutations in this gene have been associated with a hereditary form of spastic paraparesis (HSP). HSP is characterized by progressive spasticity and paralysis of the legs. There is also some evidence linking mutations in this gene with birdshot chorioretinopathy (BSCR), which results in inflammation of the choroid and retina. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

TECPR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022470057).

BP6

Variant 14-102432026-C-T is Benign according to our data. Variant chr14-102432026-C-T is described in ClinVar as [Benign]. Clinvar id is 380927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102432026-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR2	NM_014844.5 linkuse as main transcript	c.1315C>T	p.Pro439Ser	missense_variant	8/20	ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3 linkuse as main transcript	c.1315C>T	p.Pro439Ser	missense_variant	8/17		NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12 linkuse as main transcript	c.1315C>T	p.Pro439Ser	missense_variant	8/20	1	NM_014844.5	ENSP00000352510	P1	O15040-1
TECPR2	ENST00000558678.1 linkuse as main transcript	c.1315C>T	p.Pro439Ser	missense_variant	8/17	1		ENSP00000453671		O15040-2

Frequencies

GnomAD3 genomes

AF:

0.0417

AC:

6344

AN:

152192

Hom.:

157

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0571

Gnomad AMI

AF:

0.0493

Gnomad AMR

AF:

0.0454

Gnomad ASJ

AF:

0.0455

Gnomad EAS

AF:

0.0343

Gnomad SAS

AF:

0.0424

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0313

Gnomad OTH

AF:

0.0521

GnomAD3 exomes

AF:

0.0390

AC:

9512

AN:

244072

Hom.:

242

AF XY:

0.0378

AC XY:

5043

AN XY:

133346

show subpopulations

Gnomad AFR exome

AF:

0.0584

Gnomad AMR exome

AF:

0.0627

Gnomad ASJ exome

AF:

0.0488

Gnomad EAS exome

AF:

0.0288

Gnomad SAS exome

AF:

0.0369

Gnomad FIN exome

AF:

0.0375

Gnomad NFE exome

AF:

0.0303

Gnomad OTH exome

AF:

0.0402

GnomAD4 exome

AF:

0.0336

AC:

49130

AN:

1460508

Hom.:

955

Cov.:

AF XY:

0.0334

AC XY:

24277

AN XY:

726556

show subpopulations

Gnomad4 AFR exome

AF:

0.0545

Gnomad4 AMR exome

AF:

0.0604

Gnomad4 ASJ exome

AF:

0.0470

Gnomad4 EAS exome

AF:

0.0401

Gnomad4 SAS exome

AF:

0.0380

Gnomad4 FIN exome

AF:

0.0392

Gnomad4 NFE exome

AF:

0.0306

Gnomad4 OTH exome

AF:

0.0355

GnomAD4 genome

AF:

0.0417

AC:

6350

AN:

152310

Hom.:

157

Cov.:

AF XY:

0.0416

AC XY:

3099

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0571

Gnomad4 AMR

AF:

0.0454

Gnomad4 ASJ

AF:

0.0455

Gnomad4 EAS

AF:

0.0342

Gnomad4 SAS

AF:

0.0425

Gnomad4 FIN

AF:

0.0406

Gnomad4 NFE

AF:

0.0313

Gnomad4 OTH

AF:

0.0525

Alfa

AF:

0.0333

Hom.:

143

Bravo

AF:

0.0432

TwinsUK

AF:

0.0297

AC:

110

ALSPAC

AF:

0.0301

AC:

116

ESP6500AA

AF:

0.0491

AC:

203

ESP6500EA

AF:

0.0269

AC:

221

ExAC

AF:

0.0372

AC:

4479

Asia WGS

AF:

0.0480

AC:

165

AN:

3478

EpiCase

AF:

0.0334

EpiControl

AF:

0.0306

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. -

Hereditary spastic paraplegia 49

Benign:2

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Jan 15, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.68

CADD

Benign

4.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.010

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

M;M

MutationTaster

Benign

0.80

N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.086

Sift

Benign

0.41

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.036

B;.

Vest4

0.020

MPC

0.31

ClinPred

0.023

GERP RS

4.5

Varity_R

0.038

gMVP

0.26

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