rs1553212868

Variant names:

• chr1-151406263-CG-C
• rs1553212868
• NM_015100.4:c.2771delC

Your query was ambiguous. Multiple possible variants found:

• chr1-151406263-CG-C
• chr1-151406263-CG-CGG

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_015100.4(POGZ):​c.2771delC​(p.Pro924ArgfsTer4) 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 (★). Synonymous variant affecting the same amino acid position (i.e. P924P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: POGZ NM_015100.4 frameshift
• Clinical Significance: Pathogenic criteria provided, single submitter P:1
• Conservation: PhyloP100: 2.61
• Publications: 0 publications found

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]

POGZ Gene-Disease associations (from GenCC):

• intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P, Orphanet, ClinGen

ACMG classification

Our verdict: Pathogenic. The variant received 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 61 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-151406263-CG-C is Pathogenic according to our data. Variant chr1-151406263-CG-C is described in ClinVar as Pathogenic. ClinVar VariationId is 523510.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POGZ	NM_015100.4	c.2771delC	p.Pro924ArgfsTer4	frameshift_variant	Exon 19 of 19	ENST00000271715.7	NP_055915.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POGZ	ENST00000271715.7	c.2771delC	p.Pro924ArgfsTer4	frameshift_variant	Exon 19 of 19	1	NM_015100.4	ENSP00000271715.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

Submissions by phenotype

Sensorineural hearing loss disorder;C0020534:Hypertelorism;C0024433:Wide mouth;C0036572:Seizure;C0038379:Strabismus;C0221356:Brachycephaly;C0235857:Decreased lacrimation;C0240635:High palate;C0344482:Hypoplasia of the corpus callosum;C0853087:Abnormal nail morphology;C1837397:Severe global developmental delay;C1840077:Anteverted nares;C1854882:Absent speech;C1858120:Generalized hypotonia;C1859200:Inability to walk by childhood/adolescence;C1866195:Downturned corners of mouth;C4551563:Microcephaly Pathogenic:1

Jan 01, 2017

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=0/200	disease causing (ClinVar)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1553212868; hg19: chr1-151378739;