14-102428245-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014844.5(TECPR2):c.952-5G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0057 ( 30 hom. )

Consequence

TECPR2
NM_014844.5 splice_region, intron

Scores

Splicing: ADA: 0.00004091

Clinical Significance

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

Conservation

PhyloP100: -0.377

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

hereditary spastic paraplegia 49
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

TECPR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 14-102428245-G-A is Benign according to our data. Variant chr14-102428245-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 240925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00848 (226/26640) while in subpopulation NFE AF = 0.0136 (173/12714). AF 95% confidence interval is 0.012. There are 0 homozygotes in GnomAd4. There are 102 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5 link	c.952-5G>A		splice_region_variant, intron_variant	Intron 6 of 19	ENST00000359520.12	NP_055659.2	O15040-1
TECPR2	NM_001172631.3 link	c.952-5G>A		splice_region_variant, intron_variant	Intron 6 of 16		NP_001166102.1	O15040-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12 link	c.952-5G>A		splice_region_variant, intron_variant	Intron 6 of 19	1	NM_014844.5	ENSP00000352510.7		O15040-1
TECPR2	ENST00000558678.1 link	c.952-5G>A		splice_region_variant, intron_variant	Intron 6 of 16	1		ENSP00000453671.1		O15040-2

Frequencies

GnomAD3 genomes

AF:

0.00849

AC:

226

AN:

26624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00264

Gnomad AMI

AF:

0.0988

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0109

GnomAD2 exomes

AF:

0.00348

AC:

AN:

21844

AF XY:

0.00400

show subpopulations

Gnomad AFR exome

AF:

0.00126

Gnomad AMR exome

AF:

0.00483

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00140

Gnomad NFE exome

AF:

0.00469

Gnomad OTH exome

AF:

0.00922

GnomAD4 exome

AF:

0.00566

AC:

3204

AN:

565598

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

1489

AN XY:

275256

show subpopulations

African (AFR)

AF:

0.000489

AC:

AN:

12272

American (AMR)

AF:

0.00257

AC:

AN:

6992

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9446

East Asian (EAS)

AF:

0.00

AC:

AN:

18878

South Asian (SAS)

AF:

0.000133

AC:

AN:

15014

European-Finnish (FIN)

AF:

0.00114

AC:

AN:

21958

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1870

European-Non Finnish (NFE)

AF:

0.00668

AC:

3035

AN:

454516

Other (OTH)

AF:

0.00479

AC:

118

AN:

24652

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

124

248

373

497

621

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00848

AC:

226

AN:

26640

Hom.:

Cov.:

AF XY:

0.00797

AC XY:

102

AN XY:

12790

show subpopulations

African (AFR)

AF:

0.00263

AC:

AN:

7222

American (AMR)

AF:

0.00463

AC:

AN:

2374

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

656

East Asian (EAS)

AF:

0.00

AC:

AN:

1114

South Asian (SAS)

AF:

0.00

AC:

AN:

922

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

1058

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0136

AC:

173

AN:

12714

Other (OTH)

AF:

0.0106

AC:

AN:

378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.543

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000920

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 14, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TECPR2: BP4, BS2 -

Hereditary spastic paraplegia

Benign:1

Aug 16, 2021

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

Dec 12, 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

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.49

CADD

Benign

7.3

(source)

DANN

Benign

0.75

PhyloP100

-0.38

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000041

dbscSNV1_RF

Benign

0.0

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over