14-102376720-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_014844.5(TECPR2):c.-2C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0333 in 1,613,746 control chromosomes in the GnomAD database, including 1,257 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (88 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1169 hom.)
• Consequence: TECPR2 NM_014844.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.37

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]

LOC124903389 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 14-102376720-C-T is Benign according to our data. Variant chr14-102376720-C-T is described in ClinVar as [Benign]. Clinvar id is 380941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102376720-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5	c.-2C>T		5_prime_UTR_variant	2/20	ENST00000359520.12
LOC124903389	XR_007064350.1	n.73-6235G>A		intron_variant, non_coding_transcript_variant
TECPR2	NM_001172631.3	c.-2C>T		5_prime_UTR_variant	2/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12	c.-2C>T		5_prime_UTR_variant	2/20	1	NM_014844.5	P1
TECPR2	ENST00000558678.1	c.-2C>T		5_prime_UTR_variant	2/17	1
TECPR2	ENST00000561228.1	n.127C>T		non_coding_transcript_exon_variant	2/6	2

Frequencies

GnomAD3 genomes AF: 0.0264 AC: 4014 AN: 152192 Hom.: 88 Cov.: 32

Gnomad AFR AF: 0.0110

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0249

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0232

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0335

Gnomad OTH AF: 0.0259

GnomAD3 exomes AF: 0.0343 AC: 8609 AN: 251314 Hom.: 292 AF XY: 0.0393 AC XY: 5344 AN XY: 135828

Gnomad AFR exome AF: 0.00953

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.0270

Gnomad EAS exome AF: 0.000489

Gnomad SAS exome AF: 0.0977

Gnomad FIN exome AF: 0.0248

Gnomad NFE exome AF: 0.0346

Gnomad OTH exome AF: 0.0308

GnomAD4 exome AF: 0.0340 AC: 49761 AN: 1461436 Hom.: 1169 Cov.: 31 AF XY: 0.0364 AC XY: 26486 AN XY: 727032

Gnomad4 AFR exome AF: 0.0110

Gnomad4 AMR exome AF: 0.0161

Gnomad4 ASJ exome AF: 0.0278

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0984

Gnomad4 FIN exome AF: 0.0237

Gnomad4 NFE exome AF: 0.0323

Gnomad4 OTH exome AF: 0.0330

GnomAD4 genome AF: 0.0264 AC: 4014 AN: 152310 Hom.: 88 Cov.: 32 AF XY: 0.0274 AC XY: 2037 AN XY: 74476

Gnomad4 AFR AF: 0.0110

Gnomad4 AMR AF: 0.0249

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0958

Gnomad4 FIN AF: 0.0232

Gnomad4 NFE AF: 0.0335

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0295 Hom.: 39

Bravo AF: 0.0237

Asia WGS AF: 0.0400 AC: 141 AN: 3478

EpiCase AF: 0.0348

EpiControl AF: 0.0323

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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	Genome-Nilou Lab	Jul 10, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 02, 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. -

Hereditary spastic paraplegia Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Dec 08, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
Cadd	Benign	16
Dann	Benign	0.90

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

Other links and lift over

dbSNP: rs17100874; hg19: chr14-102843057;