rs104894034
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_000290.4(PGAM2):c.268C>T(p.Arg90Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,672 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000290.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PGAM2 | ENST00000297283.4 | c.268C>T | p.Arg90Trp | missense_variant | Exon 1 of 3 | 1 | NM_000290.4 | ENSP00000297283.3 | ||
DBNL | ENST00000448521.6 | c.*4346G>A | 3_prime_UTR_variant | Exon 13 of 13 | 1 | NM_001014436.3 | ENSP00000411701.1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251008Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135756
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461312Hom.: 1 Cov.: 35 AF XY: 0.0000193 AC XY: 14AN XY: 726996
GnomAD4 genome AF: 0.00000656 AC: 1AN: 152360Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74500
ClinVar
Submissions by phenotype
Glycogen storage disease type X Pathogenic:1Uncertain:1
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This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 90 of the PGAM2 protein (p.Arg90Trp). This variant is present in population databases (rs104894034, gnomAD 0.005%). This missense change has been observed in individual(s) with phosphoglycerate mutase deficiency (PMID: 8447317). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 420). 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. 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
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at