U.S. flag

An official website of the United States government

NM_018684.4(ZC4H2):c.650A>G (p.Lys217Arg) AND Wieacker-Wolff syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Apr 9, 2020
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001034718.1

Allele description [Variation Report for NM_018684.4(ZC4H2):c.650A>G (p.Lys217Arg)]

NM_018684.4(ZC4H2):c.650A>G (p.Lys217Arg)

Gene:
ZC4H2:zinc finger C4H2-type containing [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xq11.2
Genomic location:
Preferred name:
NM_018684.4(ZC4H2):c.650A>G (p.Lys217Arg)
HGVS:
  • NC_000023.11:g.64917808T>C
  • NG_021200.2:g.121937A>G
  • NM_001178032.3:c.581A>G
  • NM_001178033.3:c.487A>G
  • NM_001243804.2:c.581A>G
  • NM_018684.4:c.650A>GMANE SELECT
  • NP_001171503.1:p.Lys194Arg
  • NP_001171504.1:p.Ser163Gly
  • NP_001230733.1:p.Lys194Arg
  • NP_061154.1:p.Lys217Arg
  • NC_000023.10:g.64137688T>C
  • NM_018684.3:c.650A>G
  • NR_045044.2:n.978A>G
Protein change:
K194R; LYS217ARG
Links:
OMIM: 300897.0011; dbSNP: rs1929002470
NCBI 1000 Genomes Browser:
rs1929002470
Molecular consequence:
  • NM_001178032.3:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001178033.3:c.487A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243804.2:c.581A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018684.4:c.650A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_045044.2:n.978A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Wieacker-Wolff syndrome
Synonyms:
Wieacker syndrome; Contractures of feet, muscle atrophy, and oculomotor apraxia; Apraxia, oculomotor, with congenital contractures and muscle atrophy; See all synonyms [MedGen]
Identifiers:
Gene: 4183; MONDO: MONDO:0010758; MedGen: C0796200; Orphanet: 3454; Orphanet: 85283; OMIM: 314580

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001198008OMIM
no assertion criteria provided
Pathogenic
(Apr 9, 2020) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Deleterious de novo variants of X-linked ZC4H2 in females cause a variable phenotype with neurogenic arthrogryposis multiplex congenita.

Frints SGM, Hennig F, Colombo R, Jacquemont S, Terhal P, Zimmerman HH, Hunt D, Mendelsohn BA, Kordaß U, Webster R, Sinnema M, Abdul-Rahman O, Suckow V, Fernández-Jaén A, van Roozendaal K, Stevens SJC, Macville MVE, Al-Nasiry S, van Gassen K, Utzig N, Koudijs SM, McGregor L, et al.

Hum Mutat. 2019 Dec;40(12):2270-2285. doi: 10.1002/humu.23841. Epub 2019 Aug 21.

PubMed [citation]
PMID:
31206972
PMCID:
PMC6874899

Details of each submission

From OMIM, SCV001198008.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

In 4 affected males in a multigenerational Serbian family (family 9) with Wieacker-Wolff syndrome (WRWF; 314580), Frints et al. (2019) identified a hemizygous c.650A-G transition (c.650A-G, NM_018684.3) in exon 5 of the ZC4H2 gene, predicted to result in a lys217-to-arg (K217R) substitution at a highly conserved residue in the C terminus. The mutation, which was found by exome sequencing and confirmed by Sanger sequencing, was not found in the 1000 Genomes Project or gnomAD databases. Functional studies of the variant and studies of patient cells were not performed. There were 5 female carriers in the family, 2 of whom were over the age of 60 and had mild features.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 23, 2022