rs145635131
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_001330588.2(TPP2):āc.673A>Gā(p.Arg225Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000203 in 1,614,154 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_001330588.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPP2 | NM_001330588.2 | c.673A>G | p.Arg225Gly | missense_variant | 6/30 | ENST00000376052.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPP2 | ENST00000376052.5 | c.673A>G | p.Arg225Gly | missense_variant | 6/30 | 5 | NM_001330588.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152196Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000342 AC: 86AN: 251396Hom.: 0 AF XY: 0.000471 AC XY: 64AN XY: 135862
GnomAD4 exome AF: 0.000212 AC: 310AN: 1461840Hom.: 1 Cov.: 29 AF XY: 0.000272 AC XY: 198AN XY: 727212
GnomAD4 genome AF: 0.000112 AC: 17AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74492
ClinVar
Submissions by phenotype
Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2022 | This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 225 of the TPP2 protein (p.Arg225Gly). This variant is present in population databases (rs145635131, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with TPP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 581307). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at