dbSNP rs12434098: TECPR2:c.220-5197T>C (chr14-102402141-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014844.5(TECPR2):c.220-5197T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 152,070 control chromosomes in the GnomAD database, including 10,352 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 10352 hom., cov: 32)

Consequence

TECPR2
NM_014844.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.05

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TECPR2	NM_014844.5 link	c.220-5197T>C		intron_variant	Intron 2 of 19	ENST00000359520.12	NP_055659.2
TECPR2	NM_001172631.3 link	c.220-5197T>C		intron_variant	Intron 2 of 16		NP_001166102.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
TECPR2	ENST00000359520.12 link	c.220-5197T>C	intron_variant	Intron 2 of 19	1	NM_014844.5	ENSP00000352510.7
TECPR2	ENST00000558678.1 link	c.220-5197T>C	intron_variant	Intron 2 of 16	1		ENSP00000453671.1
TECPR2	ENST00000561228.1 link	n.348-5197T>C	intron_variant	Intron 2 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55434

AN:

151952

Hom.:

10344

Cov.:

show subpopulations

Gnomad AFR

AF:

0.338

Gnomad AMI

AF:

0.294

Gnomad AMR

AF:

0.327

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.350

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.411

Gnomad OTH

AF:

0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.365

AC:

55470

AN:

152070

Hom.:

10352

Cov.:

AF XY:

0.358

AC XY:

26641

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.338

AC:

14010

AN:

41504

American (AMR)

AF:

0.328

AC:

5001

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

1611

AN:

3470

East Asian (EAS)

AF:

0.179

AC:

925

AN:

5176

South Asian (SAS)

AF:

0.352

AC:

1692

AN:

4812

European-Finnish (FIN)

AF:

0.289

AC:

3047

AN:

10560

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.411

AC:

27962

AN:

67972

Other (OTH)

AF:

0.385

AC:

810

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1798

3596

5395

7193

8991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.395

Hom.:

2446

Bravo

AF:

0.362

Asia WGS

AF:

0.279

AC:

972

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.92

(source)

DANN

Benign

0.54

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over