rs144147210

chr14-102445811-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_014844.5(TECPR2):c.2939G>C(p.Arg980Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00248 in 1,613,744 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (3 hom., cov: 31)
  • Exomes 𝑓: 0.0024 (16 hom.)
• Consequence: TECPR2 NM_014844.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.84

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004566729).
• BP6: Variant 14-102445811-G-C is Benign according to our data. Variant chr14-102445811-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 415300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-102445811-G-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TECPR2	NM_014844.5	c.2939G>C	p.Arg980Thr	missense_variant	13/20	ENST00000359520.12
TECPR2	NM_001172631.3	c.2939G>C	p.Arg980Thr	missense_variant	13/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TECPR2	ENST00000359520.12	c.2939G>C	p.Arg980Thr	missense_variant	13/20	1	NM_014844.5	P1
TECPR2	ENST00000558678.1	c.2939G>C	p.Arg980Thr	missense_variant	13/17	1
TECPR2	ENST00000557786.1	n.548G>C		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes AF: 0.00310 AC: 471 AN: 152010 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000787

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.0271

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00212

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00348 AC: 874 AN: 251172 Hom.: 6 AF XY: 0.00345 AC XY: 469 AN XY: 135772

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000725

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000784

Gnomad FIN exome AF: 0.0226

Gnomad NFE exome AF: 0.00254

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00241 AC: 3526 AN: 1461616 Hom.: 16 Cov.: 30 AF XY: 0.00236 AC XY: 1717 AN XY: 727104

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00272

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000835

Gnomad4 FIN exome AF: 0.0216

Gnomad4 NFE exome AF: 0.00184

Gnomad4 OTH exome AF: 0.00230

GnomAD4 genome AF: 0.00310 AC: 471 AN: 152128 Hom.: 3 Cov.: 31 AF XY: 0.00411 AC XY: 306 AN XY: 74364

Gnomad4 AFR AF: 0.000241

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.0271

Gnomad4 NFE AF: 0.00212

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00216 Hom.: 3

Bravo AF: 0.00128

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00315 AC: 383

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00202

EpiControl AF: 0.00190

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 16, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	TECPR2: BP4, BS2 -

Hereditary spastic paraplegia 49 Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Hereditary spastic paraplegia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome Diagnostics Laboratory, The Hospital for Sick Children

Aug 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	18
Dann	Benign	0.93
DEOGEN2	Benign	0.0099	T;.
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.29
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.87	D;D
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	0.97	N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.028
Sift	Benign	0.61	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.42	B;.
Vest4		0.58
MVP		0.043
MPC		0.45
ClinPred		0.011	T
GERP RS		1.5
Varity_R		0.059
gMVP		0.41

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: rs144147210; hg19: chr14-102912148; COSMIC: COSV63972002; COSMIC: COSV63972002;