Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000190613 | SCV000245648 | uncertain significance | Pigmented nodular adrenocortical disease, primary, 2 | 2014-10-21 | criteria provided, single submitter | clinical testing | The p.Thr58ProfsX41 variant in PDE11A has been reported in 1 individual with adrenocortical hyperplasia and Cushing syndrome, and segregated with disease in 1 parent with hypertension, obesity, and bilaterally enlarged adrenal glands (Horvath 2006). This variant has also been reported in 1 individual with acromegaly (Peverelli 2009) and in 3 individuals with Carney complex who also carried PRKAR1A variants, and was considered to be a possible modifier of disease in these individuals (Libe 2011). This variant has been identified in 5/8254 of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). The p.Thr58ProfsX41 variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 58 and leads to a premature termination codon 41 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Several loss-of-function PDE11A variants have been described in individuals with Cushing syndrome and with adrenal hyperplasia with established loss-of-heterozygosity in somatic tissue (Horvath 2006, Carney 2010, Libe 2011). In summary, while there is some suspicion for a pathogenic role, the clinical significance of the p.Thr58ProfsX41 variant is uncertain. |
Gene |
RCV000485692 | SCV000565363 | benign | not specified | 2016-07-12 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000903265 | SCV001047723 | benign | not provided | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Broad Institute Rare Disease Group, |
RCV001258305 | SCV001435254 | likely benign | Bardet-Biedl syndrome 16 | criteria provided, single submitter | research | The c.171delT variant in PDE11A has been identified in 6 individuals with possible adrenocortical hyperplasia (PMID: 16767104, 19671705, 20351491, 21047926), and has been identified in >3% of South Asian chromosomes and 18 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 adrenocortical hyperplasia. | |
Ce |
RCV000903265 | SCV004150159 | benign | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | PDE11A: BS1, BS2 |
OMIM | RCV000190613 | SCV000025787 | uncertain significance | Pigmented nodular adrenocortical disease, primary, 2 | 2006-07-01 | no assertion criteria provided | literature only |