ClinVar Miner

Submissions for variant NM_016953.4(PDE11A):c.171del (p.Thr58fs)

gnomAD frequency: 0.00056  dbSNP: rs529789124
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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.
GeneDx 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, Broad Institute 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.
CeGaT Center for Human Genetics Tuebingen 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

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