ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.1565+5C>T

gnomAD frequency: 0.00488  dbSNP: rs41269541
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000122424 SCV000248071 benign not specified 2021-06-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000232182 SCV000288884 benign Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2024-01-31 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000282111 SCV000357784 likely benign Thrombocythemia 1 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000337044 SCV000357785 likely benign Congenital amegakaryocytic thrombocytopenia 2016-06-14 criteria provided, single submitter clinical testing
Counsyl RCV000337044 SCV000791933 uncertain significance Congenital amegakaryocytic thrombocytopenia 2017-05-31 criteria provided, single submitter clinical testing
GeneDx RCV001689671 SCV001909786 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000122424 SCV002598813 benign not specified 2022-09-16 criteria provided, single submitter clinical testing Variant summary: MPL c.1565+5C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing, however, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0046 in 279466 control chromosomes (gnomAD), predominantly at a frequency of 0.0073 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in MPL causing Congenital Amegakaryocytic Thrombocytopenia (0.0024), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.1565+5C>T in individuals affected with Congenital Amegakaryocytic Thrombocytopenia and no experimental evidence demonstrating its impact on protein function have been reported. Six ClinVar submitters have assessed the variant since 2014 without submitting evidence for clinical-significance assessments: one classified the variant as uncertain significance, one as likely benign, and four as benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen RCV001689671 SCV004123654 likely benign not provided 2024-07-01 criteria provided, single submitter clinical testing MPL: BP4, BS2
ITMI RCV000122424 SCV000083975 not provided not specified 2013-09-19 no assertion provided reference population
PreventionGenetics, part of Exact Sciences RCV004528839 SCV000311025 benign MPL-related disorder 2020-10-12 no assertion criteria provided clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Natera, Inc. RCV000337044 SCV001453983 benign Congenital amegakaryocytic thrombocytopenia 2020-09-16 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001689671 SCV002034057 likely benign not provided no assertion criteria provided clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) RCV001689671 SCV002035449 likely benign not provided no assertion criteria provided clinical testing

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