ClinVar Miner

Submissions for variant NM_005373.3(MPL):c.549G>A (p.Thr183=)

gnomAD frequency: 0.00024  dbSNP: rs147130173
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000502821 SCV000595818 likely benign not specified 2021-06-08 criteria provided, single submitter clinical testing
Invitae RCV000860898 SCV001001075 likely benign Congenital amegakaryocytic thrombocytopenia; Essential thrombocythemia 2024-01-27 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001357593 SCV004127908 likely benign not provided 2022-06-01 criteria provided, single submitter clinical testing MPL: BP4, BP7
PreventionGenetics, part of Exact Sciences RCV004541562 SCV004773808 likely benign MPL-related disorder 2023-06-14 criteria provided, single submitter clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001357593 SCV001553106 uncertain significance not provided no assertion criteria provided clinical testing The MPL p.Thr183Thr variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs147130173) and in ClinVar (classified as a VUS in 2016 by Genetics Services Laboratory, University of Chicago). The variant was identified in control databases in 114 of 282848 chromosomes (1 homozygous) at a frequency of 0.000403 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: Latino in 38 of 35438 chromosomes (freq: 0.001072), Ashkenazi Jewish in 6 of 10370 chromosomes (freq: 0.000579), European (non-Finnish) in 58 of 129164 chromosomes (freq: 0.000449), Other in 3 of 7228 chromosomes (freq: 0.000415), South Asian in 7 of 30616 chromosomes (freq: 0.000229), African in 1 of 24962 chromosomes (freq: 0.00004) and European (Finnish) in 1 of 25120 chromosomes (freq: 0.00004); it was not observed in the East Asian population. The variant occurs outside of the splicing consensus sequence however 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, GeneSplicer) predict a greater than 10% difference in splicing and the gain of a 3’ splice site. However, this information is not predictive enough to assume pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Natera, Inc. RCV001834613 SCV002086026 benign Congenital amegakaryocytic thrombocytopenia 2020-01-14 no assertion criteria provided clinical testing

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