rs139314486

Variant names:

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_014844.5(TECPR2):c.4089G>A(p.Ala1363Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,613,388 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 9 hom. )

Consequence

TECPR2
NM_014844.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.927

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 14-102498110-G-A is Benign according to our data. Variant chr14-102498110-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 385226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102498110-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.927 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5 link	c.4089G>A	p.Ala1363Ala	synonymous_variant	Exon 20 of 20	ENST00000359520.12	NP_055659.2	O15040-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TECPR2	ENST00000359520.12 link	c.4089G>A	p.Ala1363Ala	synonymous_variant	Exon 20 of 20	1	NM_014844.5	ENSP00000352510.7	O15040-1
TECPR2	ENST00000559124.1 link	n.189G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
TECPR2	ENST00000561099.1 link	n.398G>A		non_coding_transcript_exon_variant	Exon 3 of 3	2

Frequencies

GnomAD3 genomes

AF:

0.00133

AC:

202

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00238

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00152

AC:

378

AN:

249462

Hom.:

AF XY:

0.00159

AC XY:

215

AN XY:

135042

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000203

Gnomad ASJ exome

AF:

0.00349

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.0000942

Gnomad NFE exome

AF:

0.00238

Gnomad OTH exome

AF:

0.000818

GnomAD4 exome

AF:

0.00206

AC:

3008

AN:

1461078

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

1494

AN XY:

726848

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

Gnomad4 AMR exome

AF:

0.000179

Gnomad4 ASJ exome

AF:

0.00402

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.00138

Gnomad4 FIN exome

AF:

0.000568

Gnomad4 NFE exome

AF:

0.00237

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00133

AC:

202

AN:

152310

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00238

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00193

Hom.:

Bravo

AF:

0.00138

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00147

EpiControl

AF:

0.00154

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TECPR2: BP4, BP7 -

Oct 23, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary spastic paraplegia

Benign:1

Mar 01, 2018

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

TECPR2-related disorder

Benign:1

Sep 10, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hereditary spastic paraplegia 49

Benign:1

Dec 23, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.3

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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