ClinVar Miner

Submissions for variant NM_004972.4(JAK2):c.2538G>C (p.Glu846Asp)

gnomAD frequency: 0.00055  dbSNP: rs150221602
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000121242 SCV002066043 uncertain significance not specified 2021-12-16 criteria provided, single submitter clinical testing DNA sequence analysis of the JAK2 gene demonstrated a sequence change, c.2538G>C, in exon 19 that results in an amino acid change, p.Glu846Asp. This sequence change has been described in the gnomAD database with a frequency of 0.076% in the non-Finnish European subpopulation (dbSNP rs150221602). The p.Glu846Asp change affects a highly conserved amino acid residue located in a domain of the JAK2 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Glu846Asp substitution. This sequence has been previously described as a germline variant in individuals with myeloproliferative disorders in either the heterozygous or compound heterozygous state (PMID: 30259120, 273897150). An experimental study using a cellular model demonstrated that p.Glu846Asp is a weakly activating mutation (PMID: 273897150). Due to insufficient evidences, the clinical significance of the p.Glu846Asp change remains unknown at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV002517591 SCV003276013 benign not provided 2023-11-25 criteria provided, single submitter clinical testing
ITMI RCV000121242 SCV000085413 not provided not specified 2013-09-19 no assertion provided reference population

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