chr16-30748842-G-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000294.3(PHKG2):c.22G>T(p.Glu8Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,552,772 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 Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. E8E) has been classified as Likely benign.
Frequency
Consequence
NM_000294.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHKG2 | NM_000294.3 | c.22G>T | p.Glu8Ter | stop_gained | 2/10 | ENST00000563588.6 | |
PHKG2 | NM_001172432.2 | c.22G>T | p.Glu8Ter | stop_gained | 2/11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHKG2 | ENST00000563588.6 | c.22G>T | p.Glu8Ter | stop_gained | 2/10 | 1 | NM_000294.3 | P4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.00000634 AC: 1AN: 157728Hom.: 0 AF XY: 0.0000120 AC XY: 1AN XY: 83476
GnomAD4 exome AF: 0.00000143 AC: 2AN: 1400550Hom.: 0 Cov.: 32 AF XY: 0.00000289 AC XY: 2AN XY: 690944
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152222Hom.: 0 Cov.: 30 AF XY: 0.0000269 AC XY: 2AN XY: 74370
ClinVar
Submissions by phenotype
Glycogen storage disease IXc Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Mendelics | May 04, 2022 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 16, 2023 | This sequence change creates a premature translational stop signal (p.Glu8*) in the PHKG2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PHKG2 are known to be pathogenic (PMID: 8896567, 17689125, 21646031). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with phosphorylase kinase deficiency (PMID: 24389071). ClinVar contains an entry for this variant (Variation ID: 947470). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at