ClinVar Miner

Submissions for variant NM_144773.4(PROKR2):c.343G>A (p.Val115Met)

gnomAD frequency: 0.00001  dbSNP: rs138672528
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV003390830 SCV004110642 uncertain significance PROKR2-related disorder 2024-02-29 criteria provided, single submitter clinical testing The PROKR2 c.343G>A variant is predicted to result in the amino acid substitution p.Val115Met. This variant has been reported in the heterozygous state along with a PROK2 variant in individuals with Kallmann syndrome (Cole et al. 2008. PubMed ID: 18559922; Table S3, Miraoui et al. 2013. PubMed ID: 23643382). Functional studies revealed that this variant exhibits loss of function in three signaling assays when tested alone, however, in at least one signaling assay it could be rescued by WT co-transfection, which is inconsistent with a deleterious effect in the heterozygous state (Table S2, Cox et al. 2018. PubMed ID: 29161432). This variant is reported in 0.023% of alleles in individuals of South Asian descent in gnomAD. Although we suspect this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
OMIM RCV000144713 SCV000190707 pathogenic Hypogonadotropic hypogonadism 3 with or without anosmia 2008-09-01 no assertion criteria provided literature only

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