ClinVar Miner

Submissions for variant NM_144773.4(PROKR2):c.58del (p.His20fs)

dbSNP: rs587777834
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479789 SCV000567903 likely pathogenic not provided 2022-02-18 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 17054399, 23643382, 29778231, 31589614, 34426522, 24276467)
Ambry Genetics RCV000623831 SCV000740792 likely pathogenic Inborn genetic diseases 2015-01-30 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: CANDIDATE: Alteration(s) of Potential Clinical Relevance Detected
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000022409 SCV001369424 uncertain significance Hypogonadotropic hypogonadism 3 with or without anosmia 2019-05-20 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PS1.
Invitae RCV000479789 SCV001413363 pathogenic not provided 2021-08-27 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000022409 SCV001976882 uncertain significance Hypogonadotropic hypogonadism 3 with or without anosmia 2021-10-06 criteria provided, single submitter clinical testing PM2
Genetic Services Laboratory,University of Chicago RCV001818122 SCV002067427 uncertain significance not specified 2020-01-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022409 SCV002555983 pathogenic Hypogonadotropic hypogonadism 3 with or without anosmia 2022-06-17 criteria provided, single submitter clinical testing Variant summary: PROKR2 c.58delC (p.His20MetfsX24) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.0001 in 251478 control chromosomes. This frequency does not allow conclusions about variant significance. c.58delC has been reported in the literature as a heterozygous genotype in individuals from a reportedly Kallman syndrome cohort (example, Sarfati_2013), idiopathic central hypogonadism (example, Libri_2014), congenital hypogonadotropic hypogonadism (example, Abbara_2021), Obesity (example, Libri_2014) and as a compound heterozygous genotype in at-least two individuals affected with hypogonadism and anosmia whose carrier mother reported as having only anosmia (example, Dode_2006). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (VUS, n=3, Pathogenic/Likely pathogenic, n=4). Based on the evidence outlined above, the variant was classified as pathogenic.
MGZ Medical Genetics Center RCV002288460 SCV002581196 pathogenic Hypogonadotropic hypogonadism 2 with or without anosmia 2022-01-27 criteria provided, single submitter clinical testing
OMIM RCV000022409 SCV000043094 pathogenic Hypogonadotropic hypogonadism 3 with or without anosmia 2006-10-20 no assertion criteria provided literature only
PerkinElmer Genomics RCV000022409 SCV002024750 likely pathogenic Hypogonadotropic hypogonadism 3 with or without anosmia 2020-06-24 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.