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NM_005373.3(MPL):c.391+5G>C AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 25, 2024
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:
RCV001042667.8

Allele description [Variation Report for NM_005373.3(MPL):c.391+5G>C]

NM_005373.3(MPL):c.391+5G>C

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.391+5G>C
HGVS:
  • NC_000001.11:g.43338725G>C
  • NG_007525.1:g.5922G>C
  • NM_005373.3:c.391+5G>CMANE SELECT
  • LRG_510t1:c.391+5G>C
  • LRG_510:g.5922G>C
  • NC_000001.10:g.43804396G>C
  • NM_005373.2:c.391+5G>C
Links:
dbSNP: rs752453717
NCBI 1000 Genomes Browser:
rs752453717
Molecular consequence:
  • NM_005373.3:c.391+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Congenital amegakaryocytic thrombocytopenia
Identifiers:
MONDO: MONDO:0800451; MedGen: C1327915; Orphanet: 3319; OMIM: PS604498
Name:
Essential thrombocythemia
Synonyms:
essential thrombocytemia; Suspected essential thromboythemia
Identifiers:
MONDO: MONDO:0005029; MeSH: D013920; MedGen: C0040028

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001206364Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 25, 2024) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Congenital amegakaryocytic thrombocytopenia in three siblings: molecular analysis of atypical clinical presentation.

Gandhi MJ, Pendergrass TW, Cummings CC, Ihara K, Blau CA, Drachman JG.

Exp Hematol. 2005 Oct;33(10):1215-21.

PubMed [citation]
PMID:
16219544

Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization.

Buratti E, Chivers M, Královicová J, Romano M, Baralle M, Krainer AR, Vorechovsky I.

Nucleic Acids Res. 2007;35(13):4250-63. Epub 2007 Jun 18.

PubMed [citation]
PMID:
17576681
PMCID:
PMC1934990
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001206364.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change falls in intron 3 of the MPL gene. It does not directly change the encoded amino acid sequence of the MPL protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs752453717, gnomAD 0.02%). This variant has been observed in individual(s) with atypical presentation of congenital amegakaryocytic thrombocytopenia (PMID: 16219544). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372409). Studies have shown that this variant alters MPL gene expression (PMID: 16219544). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024