14-102438118-G-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014844.5(TECPR2):​c.2491G>A​(p.Gly831Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G831C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

TECPR2
NM_014844.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.091826975).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TECPR2NM_014844.5 linkc.2491G>A p.Gly831Ser missense_variant Exon 10 of 20 ENST00000359520.12 NP_055659.2 O15040-1
TECPR2NM_001172631.3 linkc.2491G>A p.Gly831Ser missense_variant Exon 10 of 17 NP_001166102.1 O15040-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TECPR2ENST00000359520.12 linkc.2491G>A p.Gly831Ser missense_variant Exon 10 of 20 1 NM_014844.5 ENSP00000352510.7 O15040-1
TECPR2ENST00000558678.1 linkc.2491G>A p.Gly831Ser missense_variant Exon 10 of 17 1 ENSP00000453671.1 O15040-2
TECPR2ENST00000560060.5 linkn.287G>A non_coding_transcript_exon_variant Exon 3 of 5 4
TECPR2ENST00000557786.1 linkn.-159G>A upstream_gene_variant 4

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
251298
AF XY:
0.00000736
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461750
Hom.:
0
Cov.:
30
AF XY:
0.00000550
AC XY:
4
AN XY:
727174
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26132
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39686
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53354
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00000540
AC:
6
AN:
1111968
Other (OTH)
AF:
0.0000331
AC:
2
AN:
60388
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.462
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000131
AC:
2
AN:
152134
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74308
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41428
American (AMR)
AF:
0.00
AC:
0
AN:
15274
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5184
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4816
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10616
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68026
Other (OTH)
AF:
0.00
AC:
0
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.600
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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:
0.00
Hom.:
0
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.059
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
16
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T;.
Eigen
Benign
-0.60
Eigen_PC
Benign
-0.42
FATHMM_MKL
Benign
0.50
N
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.0079
T
MetaRNN
Benign
0.092
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.90
L;L
PhyloP100
3.2
PrimateAI
Benign
0.34
T
PROVEAN
Benign
-1.9
N;N
REVEL
Benign
0.068
Sift
Benign
0.34
T;T
Sift4G
Benign
0.22
T;T
Polyphen
0.13
B;.
Vest4
0.23
MutPred
0.57
Gain of catalytic residue at L826 (P = 0.001);Gain of catalytic residue at L826 (P = 0.001);
MVP
0.043
MPC
0.30
ClinPred
0.15
T
GERP RS
4.0
Varity_R
0.078
gMVP
0.27
Mutation Taster
=86/14
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

Publications

Other links and lift over

dbSNP: rs201352197; hg19: chr14-102904455; API