NM_001379659.1(ZNF142):c.1892del (p.Cys631fs) AND Neurodevelopmental disorder with impaired speech and hyperkinetic movements

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 13, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000770918.13

Allele description [Variation Report for NM_001379659.1(ZNF142):c.1892del (p.Cys631fs)]

NM_001379659.1(ZNF142):c.1892del (p.Cys631fs)

Gene:

ZNF142:zinc finger protein 142 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001379659.1(ZNF142):c.1892del (p.Cys631fs)

HGVS:

NC_000002.12:g.218646330del
NG_033099.1:g.18211del
NM_001105537.4:c.1292del
NM_001366287.2:c.803del
NM_001366288.2:c.803del
NM_001366289.2:c.803del
NM_001366290.3:c.1892del
NM_001366291.2:c.1292del
NM_001379659.1:c.1892delMANE SELECT
NM_001379660.1:c.1892del
NM_001379661.1:c.1892del
NM_001379662.1:c.1292del
NP_001099007.1:p.Cys431fs
NP_001353216.1:p.Cys268fs
NP_001353217.1:p.Cys268fs
NP_001353218.1:p.Cys268fs
NP_001353219.1:p.Cys631fs
NP_001353220.1:p.Cys431fs
NP_001366588.1:p.Cys631fs
NP_001366589.1:p.Cys631fs
NP_001366590.1:p.Cys631fs
NP_001366591.1:p.Cys431fs
NC_000002.11:g.219511053del
NM_001105537.2:c.1292delG
NM_001105537.3:c.1292delG

Protein change:

C268fs

Links:

OMIM: 604083.0001; dbSNP: rs1559296368

NCBI 1000 Genomes Browser:

rs1559296368

Molecular consequence:

NM_001105537.4:c.1292del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366287.2:c.803del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366288.2:c.803del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366289.2:c.803del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366290.3:c.1892del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001366291.2:c.1292del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379659.1:c.1892del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379660.1:c.1892del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379661.1:c.1892del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001379662.1:c.1292del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Neurodevelopmental disorder with impaired speech and hyperkinetic movements
Identifiers:: MONDO: MONDO:0032741; MedGen: C5193088; OMIM: 618425

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000902417	OMIM	no assertion criteria provided	Pathogenic (May 13, 2019)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000925590	Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago	no assertion criteria provided	Likely pathogenic (Mar 8, 2019)	paternal	research	PubMed (1) [See all records that cite this PMID]
SCV001149988	Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	criteria provided, single submitter (Classification criteria August 2017)	Pathogenic (Jun 13, 2019)	paternal	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000902417

OMIM

no assertion criteria provided

Pathogenic
(May 13, 2019)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000925590

Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago

no assertion criteria provided

Likely pathogenic
(Mar 8, 2019)

paternal

research

PubMed (1)
[See all records that cite this PMID]

SCV001149988

Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München

criteria provided, single submitter

(Classification criteria August 2017)

Pathogenic
(Jun 13, 2019)

paternal

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	paternal	yes	4	1	not provided	2	yes	clinical testing, research

Citations

PubMed

Recessive variants in ZNF142 cause a complex neurodevelopmental disorder with intellectual disability, speech impairment, seizures, and dystonia.

Khan K, Zech M, Morgan AT, Amor DJ, Skorvanek M, Khan TN, Hildebrand MS, Jackson VE, Scerri TS, Coleman M, Rigbye KA, Scheffer IE, Bahlo M, Wagner M, Lam DD, Berutti R, Havránková P, Fečíková A, Strom TM, Han V, Dosekova P, Gdovinova Z, et al.

Genet Med. 2019 Nov;21(11):2532-2542. doi: 10.1038/s41436-019-0523-0. Epub 2019 Apr 30.

PubMed [citation]

PMID:: 31036918
PMCID:: PMC6821592

Details of each submission

From OMIM, SCV000902417.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 adult sisters, born of unrelated parents of Slovakian descent (family A), with neurodevelopmental disorder with impaired speech and hyperkinetic movements (NEDISHM; 618425), Khan et al. (2019) identified compound heterozygous mutations in the ZNF142 gene: a 1-bp deletion (c.1292delG, NM_001105537.2) in exon 7, predicted to result in a frameshift and premature termination (Cys431LysfsTer11), and a 2-bp deletion in exon 6 (c.817_818delAA; 604083.0002), predicted to result in a frameshift and premature termination (Lys273GlufsTer32). Both mutations were predicted to result in nonsense-mediated mRNA decay and a complete loss of function, although functional studies of the variants and studies of patient cells were not performed. The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. They were not found in the ExAC or gnomAD databases or in an in-house control exome database of 10,000 individuals.

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

From Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago, SCV000925590.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	yes	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	paternal	yes	not provided	not provided	not provided		2	not provided	1	not provided

From Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München, SCV001149988.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided
2	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	paternal	yes	1	blood	not provided		1	not provided	not provided	not provided
2	paternal	yes	1	blood	not provided		1	not provided	not provided	not provided

Last Updated: May 16, 2025

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