rs570605098
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 3P and 3B. PM2PP2BP4_ModerateBS1_Supporting
The NM_001368809.2(AMPD2):c.1192C>T(p.Arg398Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,614,024 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R398H) has been classified as Uncertain significance.
Frequency
Consequence
NM_001368809.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AMPD2 | NM_001368809.2 | c.1192C>T | p.Arg398Cys | missense_variant | 11/19 | ENST00000528667.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AMPD2 | ENST00000528667.7 | c.1192C>T | p.Arg398Cys | missense_variant | 11/19 | 1 | NM_001368809.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000269 AC: 41AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000875 AC: 22AN: 251298Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135824
GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461754Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32AN XY: 727180
GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74452
ClinVar
Submissions by phenotype
Hereditary spastic paraplegia 63 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 12, 2021 | The c.1354C>T (p.R452C) alteration is located in exon 10 (coding exon 10) of the AMPD2 gene. This alteration results from a C to T substitution at nucleotide position 1354, causing the arginine (R) at amino acid position 452 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Hereditary spastic paraplegia 63;C4014354:Pontocerebellar hypoplasia type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 452 of the AMPD2 protein (p.Arg452Cys). This variant is present in population databases (rs570605098, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with AMPD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 578069). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge - |
Pontocerebellar hypoplasia type 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at