NM_015100.4(POGZ):c.2989C>T (p.Arg997Ter) AND Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome

Germline classification:: Pathogenic/Likely pathogenic (5 submissions)
Last evaluated:: Apr 11, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001253002.8

Allele description [Variation Report for NM_015100.4(POGZ):c.2989C>T (p.Arg997Ter)]

NM_015100.4(POGZ):c.2989C>T (p.Arg997Ter)

Gene:

POGZ:pogo transposable element derived with ZNF domain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q21.3

Genomic location:

Preferred name:

NM_015100.4(POGZ):c.2989C>T (p.Arg997Ter)

HGVS:

NC_000001.11:g.151406046G>A
NG_046601.1:g.58420C>T
NM_001194937.2:c.2962C>T
NM_001194938.2:c.2803C>T
NM_015100.4:c.2989C>TMANE SELECT
NM_145796.4:c.2704C>T
NM_207171.2:c.2830C>T
NP_001181866.1:p.Arg988Ter
NP_001181867.1:p.Arg935Ter
NP_055915.2:p.Arg997Ter
NP_665739.3:p.Arg902Ter
NP_997054.1:p.Arg944Ter
NC_000001.10:g.151378522G>A
NM_015100.3:c.2989C>T

Protein change:

R902*

Links:

dbSNP: rs1553212545

NCBI 1000 Genomes Browser:

rs1553212545

Molecular consequence:

NM_001194937.2:c.2962C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001194938.2:c.2803C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_015100.4:c.2989C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_145796.4:c.2704C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_207171.2:c.2830C>T - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Intellectual disability-microcephaly-strabismus-behavioral abnormalities syndrome
Identifiers:: MONDO: MONDO:0014606; MedGen: C4225351; OMIM: 616364

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001428500	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 25, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002577545	Laboratory of Medical Genetics, National & Kapodistrian University of Athens	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 18, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002764835	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Aug 5, 2021)	de novo	clinical testing	Citation Link,
SCV004047853	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004049791	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001428500.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Laboratory of Medical Genetics, National & Kapodistrian University of Athens, SCV002577545.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

PVS1, PM2, PP3, PP5

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV002764835.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	de novo	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV004047853.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

The stop gained variant c.2989C>T (p.Arg997Ter) in POGZ gene has been reported previously in heterozygous state in patient affected with White-Sutton syndrome (Assia Batzir et al., 2020). The c.2989C>T variant is novel (not in any individuals) in gnomAD exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic/Likely_pathogenic. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. The nucleotide change c.2989C>T in POGZ is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The observed variant is present in the last exon. For these reasons, this variant has been classified as Pathogenic

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV004049791.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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