14-102445811-G-C

Variant names:

• chr14-102445811-G-C
• rs144147210
• NM_014844.5:c.2939G>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 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:6
• Conservation: PhyloP100: 1.84
• Publications: 5 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 415300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014844.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	NM_014844.5	MANE Select	c.2939G>C	p.Arg980Thr	missense	Exon 13 of 20	NP_055659.2
	TECPR2	NM_001172631.3		c.2939G>C	p.Arg980Thr	missense	Exon 13 of 17	NP_001166102.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TECPR2	ENST00000359520.12	TSL:1 MANE Select	c.2939G>C	p.Arg980Thr	missense	Exon 13 of 20	ENSP00000352510.7
	TECPR2	ENST00000558678.1	TSL:1	c.2939G>C	p.Arg980Thr	missense	Exon 13 of 17	ENSP00000453671.1
	TECPR2	ENST00000557786.1	TSL:4	n.548G>C		non_coding_transcript_exon	Exon 4 of 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

GnomAD2 exomes AF: 0.00348 AC: 874 AN: 251172 AF XY: 0.00345

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 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

African (AFR) AF: 0.000209 AC: 7 AN: 33468

American (AMR) AF: 0.000850 AC: 38 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00272 AC: 71 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.000835 AC: 72 AN: 86238

European-Finnish (FIN) AF: 0.0216 AC: 1152 AN: 53414

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00184 AC: 2045 AN: 1111842

Other (OTH) AF: 0.00230 AC: 139 AN: 60380

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

African (AFR) AF: 0.000241 AC: 10 AN: 41506

American (AMR) AF: 0.000786 AC: 12 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 12 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000416 AC: 2 AN: 4808

European-Finnish (FIN) AF: 0.0271 AC: 287 AN: 10584

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00212 AC: 144 AN: 68018

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

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:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Apr 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

TECPR2: BP4, BS2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Hereditary spastic paraplegia 49 Benign:2

Jan 19, 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

Hereditary spastic paraplegia Benign:1

Aug 01, 2018

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

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
MetaRNN	Benign	0.0046	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.8
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.028
Sift	Benign	0.61	T
Sift4G	Benign	0.12	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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

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