1-225921260-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_013328.4(PYCR2):āc.745G>Cā(p.Gly249Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Synonymous variant affecting the same amino acid position (i.e. G249G) has been classified as Likely benign.
Frequency
Consequence
NM_013328.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PYCR2 | NM_013328.4 | c.745G>C | p.Gly249Arg | missense_variant | 6/7 | ENST00000343818.11 | NP_037460.2 | |
PYCR2 | NM_001271681.2 | c.523G>C | p.Gly175Arg | missense_variant | 5/6 | NP_001258610.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PYCR2 | ENST00000343818.11 | c.745G>C | p.Gly249Arg | missense_variant | 6/7 | 1 | NM_013328.4 | ENSP00000342502.6 | ||
ENSG00000255835 | ENST00000432920.2 | c.523G>C | p.Gly175Arg | missense_variant | 5/8 | 2 | ENSP00000414068.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461756Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727200
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 05, 2022 | 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. This variant disrupts the p.Gly249 amino acid residue in PYCR2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 32330411). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 disruptive. ClinVar contains an entry for this variant (Variation ID: 1377258). This variant has not been reported in the literature in individuals affected with PYCR2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 249 of the PYCR2 protein (p.Gly249Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.