NM_005373.3(MPL):c.378del (p.Phe126fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 2023
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:: RCV001047546.7

Allele description [Variation Report for NM_005373.3(MPL):c.378del (p.Phe126fs)]

NM_005373.3(MPL):c.378del (p.Phe126fs)

Gene:

MPL:MPL proto-oncogene, thrombopoietin receptor [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_005373.3(MPL):c.378del (p.Phe126fs)

HGVS:

NC_000001.10:g.43804376del
NC_000001.11:g.43338707del
NG_007525.1:g.5904del
NM_005373.3:c.378delMANE SELECT
NP_005364.1:p.Phe126fs
NP_005364.1:p.Phe126fs
LRG_510t1:c.378del
LRG_510:g.5904del
LRG_510p1:p.Phe126fs
NC_000001.10:g.43804376del
NC_000001.10:g.43804378del
NC_000001.10:g.43804378delT
NM_005373.2:c.378del
NM_005373.2:c.378delT

Protein change:

F126fs

Links:

dbSNP: rs587778515

NCBI 1000 Genomes Browser:

rs587778515

Molecular consequence:

NM_005373.3:c.378del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001211511	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 8073287, 11133753, 16470591, 28859041, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001211511

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Thrombocytopenia in c-mpl-deficient mice.

Gurney AL, Carver-Moore K, de Sauvage FJ, Moore MW.

Science. 1994 Sep 2;265(5177):1445-7.

PubMed [citation]

PMID:: 8073287

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001211511.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Phe126Leufs*5) in the MPL gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MPL are known to be pathogenic (PMID: 8073287, 11133753). This variant is present in population databases (rs587778515, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with autosomal recessive congenital amegakaryocytic thrombocytopenia (PMID: 11133753, 16470591, 28859041). ClinVar contains an entry for this variant (Variation ID: 265249). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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