rs796052216
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_015100.4(POGZ):c.2750_2751insC(p.Pro918ThrfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
POGZ
NM_015100.4 frameshift
NM_015100.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.942
Genes affected
POGZ (HGNC:18801): (pogo transposable element derived with ZNF domain) The protein encoded by this gene appears to be a zinc finger protein containing a transposase domain at the C-terminus. This protein was found to interact with the transcription factor SP1 in a yeast two-hybrid system. Alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 51 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-151406284-T-TG is Pathogenic according to our data. Variant chr1-151406284-T-TG is described in ClinVar as [Pathogenic]. Clinvar id is 207797.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POGZ | NM_015100.4 | c.2750_2751insC | p.Pro918ThrfsTer26 | frameshift_variant | 19/19 | ENST00000271715.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POGZ | ENST00000271715.7 | c.2750_2751insC | p.Pro918ThrfsTer26 | frameshift_variant | 19/19 | 1 | NM_015100.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 35
GnomAD4 exome
Cov.:
35
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 06, 2016 | The c.2750dupC variant in the POGZ gene has been published as a pathogenic variant associated with POGZ-related disorders (Ye et al., 2015). The c.2750dupC variant causes a frameshift starting with codon Proline 918, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Pro918ThrfsX26. This variant is predicted to cause loss of normal protein function through protein truncation. The c.2750dupC variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.2750dupC as a pathogenic variant. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at