rs749351336
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_014844.5(TECPR2):c.1800G>A(p.Glu600Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,430,552 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TECPR2
NM_014844.5 synonymous
NM_014844.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.122
Publications
0 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 49Inheritance: 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: Likely_benign. The variant received -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 14-102434617-G-A is Benign according to our data. Variant chr14-102434617-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 415303.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.122 with no splicing effect.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| TECPR2 | ENST00000359520.12 | c.1800G>A | p.Glu600Glu | synonymous_variant | Exon 9 of 20 | 1 | NM_014844.5 | ENSP00000352510.7 | ||
| TECPR2 | ENST00000558678.1 | c.1800G>A | p.Glu600Glu | synonymous_variant | Exon 9 of 17 | 1 | ENSP00000453671.1 | |||
| TECPR2 | ENST00000560060.5 | n.-222G>A | upstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000860 AC: 2AN: 232578 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
232578
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000140 AC: 2AN: 1430552Hom.: 0 Cov.: 30 AF XY: 0.00000141 AC XY: 1AN XY: 706742 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1430552
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
706742
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
33040
American (AMR)
AF:
AC:
0
AN:
43328
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24044
East Asian (EAS)
AF:
AC:
1
AN:
39294
South Asian (SAS)
AF:
AC:
1
AN:
81636
European-Finnish (FIN)
AF:
AC:
0
AN:
52248
Middle Eastern (MID)
AF:
AC:
0
AN:
5642
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1092286
Other (OTH)
AF:
AC:
0
AN:
59034
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0448430), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.350
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
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
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Hereditary spastic paraplegia 49 Benign:1
Nov 20, 2023
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.