rs62000389

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014844.5(TECPR2):c.2941C>A(p.Gln981Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 1,613,582 control chromosomes in the GnomAD database, including 361 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 24 hom., cov: 31)

Exomes 𝑓: 0.020 ( 337 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.71

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=0.006488502).

BP6

Variant 14-102445813-C-A is Benign according to our data. Variant chr14-102445813-C-A is described in ClinVar as [Benign]. Clinvar id is 240924.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102445813-C-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0142 (2159/152076) while in subpopulation NFE AF= 0.0211 (1433/68000). AF 95% confidence interval is 0.0202. There are 24 homozygotes in gnomad4. There are 1027 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5 linkuse as main transcript	c.2941C>A	p.Gln981Lys	missense_variant	13/20	ENST00000359520.12
TECPR2	NM_001172631.3 linkuse as main transcript	c.2941C>A	p.Gln981Lys	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12 linkuse as main transcript	c.2941C>A	p.Gln981Lys	missense_variant	13/20	1	NM_014844.5	P1	O15040-1
TECPR2	ENST00000558678.1 linkuse as main transcript	c.2941C>A	p.Gln981Lys	missense_variant	13/17	1			O15040-2
TECPR2	ENST00000557786.1 linkuse as main transcript	n.550C>A		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2158

AN:

151958

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00435

Gnomad AMI

AF:

0.0795

Gnomad AMR

AF:

0.00729

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0185

Gnomad FIN

AF:

0.0142

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0211

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.0172

AC:

4327

AN:

251142

Hom.:

AF XY:

0.0184

AC XY:

2504

AN XY:

135766

show subpopulations

Gnomad AFR exome

AF:

0.00449

Gnomad AMR exome

AF:

0.00612

Gnomad ASJ exome

AF:

0.0283

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0218

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0234

Gnomad OTH exome

AF:

0.0193

GnomAD4 exome

AF:

0.0199

AC:

29031

AN:

1461506

Hom.:

337

Cov.:

AF XY:

0.0200

AC XY:

14566

AN XY:

727064

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.00687

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0217

Gnomad4 FIN exome

AF:

0.0135

Gnomad4 NFE exome

AF:

0.0215

Gnomad4 OTH exome

AF:

0.0176

GnomAD4 genome

AF:

0.0142

AC:

2159

AN:

152076

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1027

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00439

Gnomad4 AMR

AF:

0.00728

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0183

Gnomad4 FIN

AF:

0.0142

Gnomad4 NFE

AF:

0.0211

Gnomad4 OTH

AF:

0.0132

Alfa

AF:

0.0203

Hom.:

Bravo

AF:

0.0136

TwinsUK

AF:

0.0227

AC:

ALSPAC

AF:

0.0249

AC:

ESP6500AA

AF:

0.00545

AC:

ESP6500EA

AF:

0.0221

AC:

190

ExAC

AF:

0.0183

AC:

2219

Asia WGS

AF:

0.00982

AC:

AN:

3478

EpiCase

AF:

0.0199

EpiControl

AF:

0.0221

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 01, 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, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Hereditary spastic paraplegia 49

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 26, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

Hereditary spastic paraplegia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Nov 23, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.30

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.036

T;.

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;D

MetaRNN

Benign

0.0065

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

2.9

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.24

Sift

Benign

0.047

D;D

Sift4G

Uncertain

0.022

D;D

Polyphen

1.0

D;.

Vest4

0.21

MPC

0.57

ClinPred

0.036

GERP RS

5.3

Varity_R

0.36

gMVP

0.78

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