Variant 14-102428245-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_014844.5(TECPR2):c.952-5G>T variant causes a splice region, splice polypyrimidine tract, 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 0.039 ( 0 hom., cov: 0)

Exomes 𝑓: 0.13 ( 22 hom. )

Failed GnomAD Quality Control

Consequence

TECPR2
NM_014844.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00004718

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.377

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 14-102428245-G-T is Benign according to our data. Variant chr14-102428245-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 702193.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TECPR2	NM_014844.5 linkuse as main transcript	c.952-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3 linkuse as main transcript	c.952-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TECPR2	ENST00000359520.12 linkuse as main transcript	c.952-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_014844.5	ENSP00000352510	P1	O15040-1
TECPR2	ENST00000558678.1 linkuse as main transcript	c.952-5G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000453671		O15040-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

1020

AN:

25938

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0388

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0313

Gnomad EAS

AF:

0.0215

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.0135

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0453

Gnomad OTH

AF:

0.0328

GnomAD3 exomes

AF:

0.00449

AC:

AN:

21844

Hom.:

AF XY:

0.00434

AC XY:

AN XY:

11990

show subpopulations

Gnomad AFR exome

AF:

0.00692

Gnomad AMR exome

AF:

0.0145

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.00672

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.000935

Gnomad NFE exome

AF:

0.00280

Gnomad OTH exome

AF:

0.0115

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.132

AC:

62206

AN:

472908

Hom.:

Cov.:

AF XY:

0.128

AC XY:

29602

AN XY:

231568

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0226

Gnomad4 ASJ exome

AF:

0.0527

Gnomad4 EAS exome

AF:

0.0124

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.00997

Gnomad4 NFE exome

AF:

0.151

Gnomad4 OTH exome

AF:

0.0987

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0393

AC:

1020

AN:

25954

Hom.:

Cov.:

AF XY:

0.0359

AC XY:

449

AN XY:

12498

show subpopulations

Gnomad4 AFR

AF:

0.0386

Gnomad4 AMR

AF:

0.0293

Gnomad4 ASJ

AF:

0.0313

Gnomad4 EAS

AF:

0.0217

Gnomad4 SAS

AF:

0.0519

Gnomad4 FIN

AF:

0.0135

Gnomad4 NFE

AF:

0.0453

Gnomad4 OTH

AF:

0.0319

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hereditary spastic paraplegia 49

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

DANN

Benign

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.010

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