NM_005373.3(MPL):c.1666G>T (p.Val556Phe) AND Congenital amegakaryocytic thrombocytopenia

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jul 12, 2017
Review status:: criteria provided, conflicting classifications

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:: RCV000363866.8

Allele description [Variation Report for NM_005373.3(MPL):c.1666G>T (p.Val556Phe)]

NM_005373.3(MPL):c.1666G>T (p.Val556Phe)

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.1666G>T (p.Val556Phe)

HGVS:

NC_000001.11:g.43352530G>T
NG_007525.1:g.19727G>T
NM_005373.3:c.1666G>TMANE SELECT
NP_005364.1:p.Val556Phe
NP_005364.1:p.Val556Phe
LRG_510t1:c.1666G>T
LRG_510:g.19727G>T
LRG_510p1:p.Val556Phe
NC_000001.10:g.43818201G>T
NM_005373.2:c.1666G>T

Protein change:

V556F

Links:

dbSNP: rs150004498

NCBI 1000 Genomes Browser:

rs150004498

Molecular consequence:

NM_005373.3:c.1666G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Congenital amegakaryocytic thrombocytopenia
Identifiers:: MONDO: MONDO:0800451; MedGen: C1327915; Orphanet: 3319; OMIM: PS604498

Recent activity

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ALG6 [Candida albicans SC5314]
ALG6 [Candida albicans SC5314]
Gene ID:3647316

Gene
LOC4327591 [Oryza sativa Japonica Group]
LOC4327591 [Oryza sativa Japonica Group]
Gene ID:4327591

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000357794	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Likely benign (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV000792764	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Jul 12, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000357794

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Likely benign
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV000792764

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Jul 12, 2017)

unknown

clinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Elevated thrombopoietin levels and alterations in the sequence of its receptor, c-Mpl, in patients with Diamond-Blackfan anemia.

Pospisilova D, Cmejlova J, Slavik L, Cmejla R.

Haematologica. 2004 Nov;89(11):1391-2.

PubMed [citation]

PMID:: 15531462

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000357794.3

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

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

#	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

From Counsyl, SCV000792764.1

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

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

Last Updated: Sep 29, 2024

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