ClinVar Miner

Submissions for variant NM_000250.2(MPO):c.2031-2A>C (rs35897051)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000003816 SCV000221199 pathogenic Myeloperoxidase deficiency 2014-09-26 criteria provided, single submitter clinical testing The 2031-2A>C variant in MPO has been previously identified in 1 compound heterozygous and 2 homozygous individuals with myeloperoxidase deficiency (Marchetti 2004). This variant is located in the 3' splice region and functional studies indicate that this variant leads to altered splicing (Marchetti 2004). In summary, the 2031-2A>C variant meets our criteria to be considered causative for myeloperoxidase deficiency (MPOD) in a recessive manner. However, the clinical relevance of MPOD is not well-established.
GeneDx RCV000265536 SCV000329427 pathogenic not provided 2018-05-04 criteria provided, single submitter clinical testing The c.2031-2A>C pathogenic variant in the MPO gene has been reported previously in association with myeloperoxidase deficiency, when present in the homozygous state or when in trans with another disease-causing variant (Marchetti et al., 2004; Mauch et al., 2007). This splice site variant destroys the canonical splice acceptor site in intron 11, and causes the activation of a cryptic splice site located 109 nucleotides upstream of the authentic splice site (Marchetti et al., 2004). The 109 nucleotide insertion causes a shift in the reading frame that is predicted to lead to the generation of an abnormal MPO precursor lacking enzymatic activity (Marchetti et al., 2004). The c.2031-2A>C variant is observed in 470/66434 (0.7%) alleles from individuals of non-Finnish European background, including one homozygous individual, in the ExAC dataset (Lek et al., 2016). We interpret c.2031-2A>C as a pathogenic variant.
OMIM RCV000003816 SCV000023981 pathogenic Myeloperoxidase deficiency 2004-05-01 no assertion criteria provided literature only
GenomeConnect, ClinGen RCV000003816 SCV000607007 not provided Myeloperoxidase deficiency no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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