ClinVar Miner

Submissions for variant NM_000250.2(MPO):c.995C>T (p.Ala332Val)

gnomAD frequency: 0.01176  dbSNP: rs28730837
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000003814 SCV001140700 uncertain significance Myeloperoxidase deficiency 2019-05-28 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000003814 SCV001435274 likely benign Myeloperoxidase deficiency criteria provided, single submitter research The heterozygous p.Ala332Val variant in MPO has been identified in 2 individuals with myeloperoxidase deficiency (PMID: 15108282), but has also been identified in >4% of European (Finnish) chromosomes and 27 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal recessive myeloperoxidase deficiency.
CeGaT Center for Human Genetics Tuebingen RCV002510767 SCV002822414 benign not provided 2022-10-01 criteria provided, single submitter clinical testing MPO: BS1, BS2
OMIM RCV000003814 SCV000023979 pathogenic Myeloperoxidase deficiency 2004-05-01 no assertion criteria provided literature only
Reproductive Health Research and Development, BGI Genomics RCV000003814 SCV001142476 uncertain significance Myeloperoxidase deficiency 2020-01-06 no assertion criteria provided curation NM_000250.1:c.995C>T in the MPO gene has an allele frequency of 0.043 in European (Finnish) subpopulation in the gnomAD database. Mutations in the MPO gene lead to Hereditary myeloperoxidase (MPO) deficiency in an autosomal recessive manner. Although a number of 45 homozygous occurrences is observed in the gnomAD database, the majority patients with myeloperoxidase deficiency are asymptomatic clinically except if they are also diabetic. Therefore we determined not to adapt this as a strong benign evidence. Marchetti et al. identified a individual with a partial myeloperoxidase deficiency, harboring the compound heterozygote for this variant and c.1715T>G (PMID: 15108282). Conservatively, we interpret it as variant of uncertain significance (VUS). ACMG/AMP criteria applied: PM3, PP4, BS1.

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