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NM_000460.4(THPO):c.469C>T (p.Arg157Ter) AND Amegakaryocytic thrombocytopenia, congenital, 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 5, 2023
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:
RCV003325579.3

Allele description [Variation Report for NM_000460.4(THPO):c.469C>T (p.Arg157Ter)]

NM_000460.4(THPO):c.469C>T (p.Arg157Ter)

Gene:
THPO:thrombopoietin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3q27.1
Genomic location:
Preferred name:
NM_000460.4(THPO):c.469C>T (p.Arg157Ter)
HGVS:
  • NC_000003.12:g.184373106G>A
  • NG_012136.1:g.10039C>T
  • NM_000460.4:c.469C>TMANE SELECT
  • NM_001177597.2:c.457C>T
  • NM_001177598.2:c.452C>T
  • NM_001289997.1:c.469C>T
  • NM_001289998.1:c.469C>T
  • NM_001290003.1:c.889C>T
  • NM_001290022.1:c.457C>T
  • NM_001290026.1:c.452C>T
  • NM_001290027.1:c.469C>T
  • NM_001290028.1:c.469C>T
  • NP_000451.1:p.Arg157Ter
  • NP_001171068.1:p.Arg153Ter
  • NP_001171069.1:p.Pro151Leu
  • NP_001276926.1:p.Arg157Ter
  • NP_001276927.1:p.Arg157Ter
  • NP_001276932.1:p.Arg297Ter
  • NP_001276951.1:p.Arg153Ter
  • NP_001276955.1:p.Pro151Leu
  • NP_001276956.1:p.Arg157Ter
  • NP_001276957.1:p.Arg157Ter
  • LRG_580t1:c.469C>T
  • LRG_580:g.10039C>T
  • LRG_580p1:p.Arg157Ter
  • NC_000003.11:g.184090894G>A
Protein change:
P151L; ARG157TER
Links:
OMIM: 600044.0010; dbSNP: rs1412486198
NCBI 1000 Genomes Browser:
rs1412486198
Molecular consequence:
  • NM_001177598.2:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001290026.1:c.452C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000460.4:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001177597.2:c.457C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289997.1:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289998.1:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001290003.1:c.889C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001290022.1:c.457C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001290027.1:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001290028.1:c.469C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Amegakaryocytic thrombocytopenia, congenital, 2 (CAMT2)
Identifiers:
MONDO: MONDO:0957575; MedGen: C5882679; OMIM: 620481

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004030507OMIM
no assertion criteria provided
Pathogenic
(Sep 5, 2023) 		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

Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin.

Seo A, Ben-Harosh M, Sirin M, Stein J, Dgany O, Kaplelushnik J, Hoenig M, Pannicke U, Lorenz M, Schwarz K, Stockklausner C, Walsh T, Gulsuner S, Lee MK, Sendamarai A, Sanchez-Bonilla M, King MC, Cario H, Kulozik AE, Debatin KM, Schulz A, Tamary H, et al.

Blood. 2017 Aug 17;130(7):875-880. doi: 10.1182/blood-2017-02-768036. Epub 2017 May 30.

PubMed [citation]
PMID:
28559357
PMCID:
PMC5561901

Details of each submission

From OMIM, SCV004030507.2

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

Description

In a girl, born of consanguineous Saudi Arabian parents (family C), with congenital amegakaryocytic thrombocytopenia-2 (CAMT2; 620481), Seo et al. (2017) identified a homozygous c.469C-T transition (c.469C-T, NM_000460.3) in the THPO gene, resulting in an arg157-to-ter (R157X) substitution in the middle of the protein, predicted to result in absence of the C-terminal glycan domain. The mutation, which was found by whole-exome sequencing, segregated with the disorder in the family and was not present in public databases, including dbSNP (build 141), Exome Variant Server, 1000 Genomes Project, and ExAC. Functional studies of the variant were not performed, but it was predicted to result in a loss of function. Serum THPO levels were undetectable in the patient.

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

Last Updated: Aug 4, 2024