ClinVar Miner

Submissions for variant NM_144773.4(PROKR2):c.743G>A (p.Arg248Gln)

gnomAD frequency: 0.00008  dbSNP: rs376142095
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001140929 SCV001301235 benign Hypogonadotropic hypogonadism 3 with or without anosmia 2017-07-26 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV002514778 SCV003243011 uncertain significance not provided 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 248 of the PROKR2 protein (p.Arg248Gln). This variant is present in population databases (rs376142095, gnomAD 0.03%). This missense change has been observed in individual(s) with PROKR2-related conditions (PMID: 18559922, 25759380). ClinVar contains an entry for this variant (Variation ID: 156565). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt PROKR2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect PROKR2 function (PMID: 29161432). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV001140929 SCV005660810 uncertain significance Hypogonadotropic hypogonadism 3 with or without anosmia 2024-03-28 criteria provided, single submitter clinical testing
OMIM RCV000144715 SCV000190709 pathogenic Hypogonadotropic hypogonadism 3 without anosmia 2008-09-01 no assertion criteria provided literature only

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