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NM_001372123.1(IKZF5):c.418T>C (p.Cys140Arg) AND Thrombocytopenia 7

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Dec 23, 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:
RCV002245462.4

Allele description [Variation Report for NM_001372123.1(IKZF5):c.418T>C (p.Cys140Arg)]

NM_001372123.1(IKZF5):c.418T>C (p.Cys140Arg)

Gene:
IKZF5:IKAROS family zinc finger 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q26.13
Genomic location:
Preferred name:
NM_001372123.1(IKZF5):c.418T>C (p.Cys140Arg)
HGVS:
  • NC_000010.11:g.122994622A>G
  • NG_067239.1:g.19174T>C
  • NM_001271840.1:c.418T>C
  • NM_001372123.1:c.418T>CMANE SELECT
  • NM_001372124.1:c.214T>C
  • NM_001372125.1:c.418T>C
  • NM_001372126.1:c.418T>C
  • NM_001372127.1:c.418T>C
  • NM_001372128.1:c.418T>C
  • NM_001372129.1:c.214T>C
  • NM_001372130.1:c.214T>C
  • NM_001372131.1:c.214T>C
  • NP_001258769.1:p.Cys140Arg
  • NP_001359052.1:p.Cys140Arg
  • NP_001359053.1:p.Cys72Arg
  • NP_001359054.1:p.Cys140Arg
  • NP_001359055.1:p.Cys140Arg
  • NP_001359056.1:p.Cys140Arg
  • NP_001359057.1:p.Cys140Arg
  • NP_001359058.1:p.Cys72Arg
  • NP_001359059.1:p.Cys72Arg
  • NP_001359060.1:p.Cys72Arg
  • LRG_1429t1:c.418T>C
  • LRG_1429:g.19174T>C
  • LRG_1429p1:p.Cys140Arg
  • NC_000010.10:g.124754138A>G
Protein change:
C140R; CYS140ARG
Links:
OMIM: 606238.0002; dbSNP: rs2133379859
NCBI 1000 Genomes Browser:
rs2133379859
Molecular consequence:
  • NM_001271840.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372123.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372124.1:c.214T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372125.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372126.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372127.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372128.1:c.418T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372129.1:c.214T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372130.1:c.214T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001372131.1:c.214T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Thrombocytopenia 7
Synonyms:
THROMBOCYTOPENIA, AUTOSOMAL DOMINANT, 7
Identifiers:
MONDO: MONDO:0030867; MedGen: C5436874; OMIM: 619130

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001451914OMIM
no assertion criteria provided
Pathogenic
(Dec 23, 2020) 		germlineliterature only

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

SCV002515731ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology
no assertion criteria provided
Pathogenicde novoresearch

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyesnot providednot providednot providednot providedyesresearch
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Germline mutations in the transcription factor IKZF5 cause thrombocytopenia.

Lentaigne C, Greene D, Sivapalaratnam S, Favier R, Seyres D, Thys C, Grassi L, Mangles S, Sibson K, Stubbs M, Burden F, Bordet JC, Armari-Alla C, Erber W, Farrow S, Gleadall N, Gomez K, Megy K, Papadia S, Penkett CJ, Sims MC, Stefanucci L, et al.

Blood. 2019 Dec 5;134(23):2070-2081. doi: 10.1182/blood.2019000782.

PubMed [citation]
PMID:
31217188

Details of each submission

From OMIM, SCV001451914.1

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

Description

In monozygotic twin sisters (family B) with thrombocytopenia-7 (THC7; 619130), Lentaigne et al. (2019) identified a de novo heterozygous mutation in the IKZF5 gene, resulting in a cys140-to-arg (C140R) substitution at a highly conserved residue within one of the N-terminal zinc finger domains. The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, was not present in the gnomAD database. In vitro functional expression studies in transfected HEK293 cells showed that the mutant protein tended to remain in the cytosol instead of entering the nucleus; the mutant protein also showed impaired chromatin binding compared to controls.

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

From ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV002515731.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providedyesresearchnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2024