NM_005373.3(MPL):c.127C>T (p.Arg43Ter) AND Congenital amegakaryocytic thrombocytopenia

Clinical significance:Pathogenic (Last evaluated: Oct 25, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000411190.2

Allele description [Variation Report for NM_005373.3(MPL):c.127C>T (p.Arg43Ter)]

NM_005373.3(MPL):c.127C>T (p.Arg43Ter)

Gene:
MPL:MPL proto-oncogene, thrombopoietin receptor [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.2
Genomic location:
Preferred name:
NM_005373.3(MPL):c.127C>T (p.Arg43Ter)
HGVS:
  • NC_000001.11:g.43338146C>T
  • NG_007525.1:g.5343C>T
  • NM_005373.2:c.127C>T
  • NM_005373.3:c.127C>TMANE SELECT
  • NP_005364.1:p.Arg43Ter
  • NP_005364.1:p.Arg43Ter
  • LRG_510t1:c.127C>T
  • LRG_510:g.5343C>T
  • LRG_510p1:p.Arg43Ter
  • NC_000001.10:g.43803817C>T
Protein change:
R43*
Links:
dbSNP: rs148434485
NCBI 1000 Genomes Browser:
rs148434485
Molecular consequence:
  • NM_005373.2:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_005373.3:c.127C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Congenital amegakaryocytic thrombocytopenia (CAMT)
Identifiers:
MONDO: MONDO:0011469; MedGen: C1327915; Orphanet: 3319; OMIM: 604498

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000487190Counsylcriteria provided, single submitter
Pathogenic
(Oct 31, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV002015069Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Oct 25, 2021)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia.

Ballmaier M, Germeshausen M, Schulze H, Cherkaoui K, Lang S, Gaudig A, Krukemeier S, Eilers M, Strauss G, Welte K.

Blood. 2001 Jan 1;97(1):139-46.

PubMed [citation]
PMID:
11133753

MPL mutations in 23 patients suffering from congenital amegakaryocytic thrombocytopenia: the type of mutation predicts the course of the disease.

Germeshausen M, Ballmaier M, Welte K.

Hum Mutat. 2006 Mar;27(3):296.

PubMed [citation]
PMID:
16470591
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000487190.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002015069.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: MPL c.127C>T (p.Arg43X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 3.2e-05 in 251424 control chromosomes. c.127C>T has been reported in the literature in multiple individuals affected with Congenital Amegakaryocytic Thrombocytopenia (example, Ballmaier_2001, Germeshausen_2006). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 20, 2021

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