NM_005373.3(MPL):c.391+5G>C AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 12, 2018
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:: RCV000825643.6

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]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000967013	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jan 12, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16219544, 11972523, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000967013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jan 12, 2018)

germline

clinical testing

PubMed (3)
[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	not provided	1	1	not provided	not provided	not provided	clinical 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

Three parameters, plasma thrombopoietin levels, plasma glycocalicin levels and megakaryocyte culture, distinguish between different causes of congenital thrombocytopenia.

van den Oudenrijn S, Bruin M, Folman CC, Bussel J, de Haas M, von dem Borne AE.

Br J Haematol. 2002 May;117(2):390-8.

PubMed [citation]

PMID:: 11972523

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000967013.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (3)

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The c.391+5G>C variant in MPL has been reported in 3 members of 1 family with congenital amegak aryocytic thrombocytopenia (CAMT), all of whom carried a pathogenic variant on t he other MPL allele (Gandhi 2005). The c.391+5G>C variant has also been identifi ed in 27/126592 European chromsomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs752453717). Although this variant has been seen in the general population, its frequency is low enough to be consisten t with a recessive carrier frequency. This variant is located in the 5' splice r egion. While in vitro functional studies suggest an impact to splicing (Gandhi 2 005), these types of assays may not accurately represent biological function. In summary, while there is some suspicion for a pathogenic role, the clinical sign ificance of the c.391+5G>C variant is uncertain. ACMG/AMP Criteria applied: PM2; PVS1_Supporting; PP1_Moderate.

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

Last Updated: Sep 29, 2024

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