rs11845676

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014844.5(TECPR2):c.1156G>A(p.Ala386Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0118 in 1,603,288 control chromosomes in the GnomAD database, including 613 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 Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 306 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 307 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.654

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 49
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

TECPR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0017033517).

BP6

Variant 14-102431867-G-A is Benign according to our data. Variant chr14-102431867-G-A is described in ClinVar as [Benign]. Clinvar id is 415302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5 link	c.1156G>A	p.Ala386Thr	missense_variant	Exon 8 of 20	ENST00000359520.12	NP_055659.2	O15040-1
TECPR2	NM_001172631.3 link	c.1156G>A	p.Ala386Thr	missense_variant	Exon 8 of 17		NP_001166102.1	O15040-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12 link	c.1156G>A	p.Ala386Thr	missense_variant	Exon 8 of 20	1	NM_014844.5	ENSP00000352510.7		O15040-1
TECPR2	ENST00000558678.1 link	c.1156G>A	p.Ala386Thr	missense_variant	Exon 8 of 17	1		ENSP00000453671.1		O15040-2

Frequencies

GnomAD3 genomes

AF:

0.0382

AC:

5817

AN:

152204

Hom.:

306

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00561

Gnomad OTH

AF:

0.0315

GnomAD2 exomes

AF:

0.0138

AC:

3437

AN:

248572

AF XY:

0.0113

show subpopulations

Gnomad AFR exome

AF:

0.123

Gnomad AMR exome

AF:

0.0106

Gnomad ASJ exome

AF:

0.0244

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00153

Gnomad NFE exome

AF:

0.00587

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00904

AC:

13115

AN:

1450966

Hom.:

307

Cov.:

AF XY:

0.00838

AC XY:

6027

AN XY:

719078

show subpopulations

African (AFR)

AF:

0.121

AC:

4014

AN:

33272

American (AMR)

AF:

0.0122

AC:

541

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.0249

AC:

649

AN:

26056

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39354

South Asian (SAS)

AF:

0.00258

AC:

222

AN:

85972

European-Finnish (FIN)

AF:

0.00152

AC:

AN:

53250

Middle Eastern (MID)

AF:

0.00907

AC:

AN:

5732

European-Non Finnish (NFE)

AF:

0.00613

AC:

6762

AN:

1103078

Other (OTH)

AF:

0.0133

AC:

793

AN:

59778

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

743

1487

2230

2974

3717

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0382

AC:

5822

AN:

152322

Hom.:

306

Cov.:

AF XY:

0.0370

AC XY:

2753

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.119

AC:

4960

AN:

41564

American (AMR)

AF:

0.0191

AC:

293

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0248

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.00331

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00562

AC:

382

AN:

68032

Other (OTH)

AF:

0.0312

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

263

526

790

1053

1316

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0136

Hom.:

163

Bravo

AF:

0.0439

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.123

AC:

541

ESP6500EA

AF:

0.00721

AC:

ExAC

AF:

0.0157

AC:

1910

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.00763

EpiControl

AF:

0.00753

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary spastic paraplegia 49

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:1

Apr 20, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Hereditary spastic paraplegia

Benign:1

Dec 10, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.71

CADD

Benign

5.7

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.0022

T;.

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.57

T;T

MetaRNN

Benign

0.0017

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.79

N;N

PhyloP100

0.65

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.21

N;N

REVEL

Benign

0.043

Sift

Benign

0.54

T;T

Sift4G

Benign

0.64

T;T

Polyphen

0.0010

B;.

Vest4

0.021

MPC

0.30

ClinPred

0.0024

GERP RS

4.2

Varity_R

0.025

gMVP

0.26

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs11845676

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over