Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UCLA Clinical Genomics Center, |
RCV000196772 | SCV000255325 | pathogenic | Partial androgen insensitivity syndrome | 2014-07-01 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000499525 | SCV000593280 | benign | not specified | 2016-09-22 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000990850 | SCV001141898 | benign | Androgen resistance syndrome | 2024-02-28 | criteria provided, single submitter | clinical testing | |
Clinical Genetics and Genomics, |
RCV001269900 | SCV001450250 | pathogenic | not provided | 2014-08-20 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001516905 | SCV001725277 | benign | Androgen resistance syndrome; Kennedy disease | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Pars Genome Lab | RCV002221510 | SCV002098054 | benign | Androgen resistance syndrome; Partial androgen insensitivity syndrome | 2022-02-21 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001269900 | SCV004165241 | benign | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | AR: PP3, BS1, BS2 |
Clinical Biochemistry Laboratory, |
RCV000990850 | SCV004190290 | likely benign | Androgen resistance syndrome | 2023-11-20 | criteria provided, single submitter | clinical testing | ACMG:PM1 PP3 BS1 BP2 BP4 |
Foundation for Research in Genetics and Endocrinology, |
RCV000627669 | SCV000746022 | uncertain significance | Hypospadias 1, X-linked | 2018-01-31 | no assertion criteria provided | clinical testing | The observed variant c.1174C>T (p.P392S) has the minor allele frequency of 0.74% in 1000 Genomes and 0.8% in ExAC databases. The in silico predictions of the variant is polymorphism by Mutation Taster, benign by PolyPhen and damaging by SIFT. |
Department of Pathology and Laboratory Medicine, |
RCV001269900 | SCV001549096 | likely benign | not provided | no assertion criteria provided | clinical testing | The AR p.Pro392Ser variant was identified in 4 of 584 proband chromosomes (frequency: 0.00685) from a Caucasian population presenting with isolated hypospadias without micropenis or cryptorchidism, and was not identified in 690 control chromosomes from healthy individuals (Kalfa_2013_23637914). The variant was also identified in dbSNP (ID: rs201934623) as "With Pathogenic allele" and ClinVar (3 submissions with conflicting interpretations of pathogenicity: Benign(1) by Genetic Services Laboratory, University of Chicago (2016); Pathogenic(1) by UCLA Clinical Genomics Center, UCLA - CES (2014); and Uncertain significance(1) by Foundation for Research in Genetics and Endocrinology, Institute of Human Genetics (2018)). Submitters report the variant to be linked to Partial Androgen Insensitivity syndrome and Hypospadias 1, X-linked. The variant was also identified in Clinvitae, Cosmic, MutDB, and LOVD 3.0 (likely benign). The variant was identified in control databases in 684 of 166808 chromosomes (4 homozygous) at a frequency of 0.004101 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: South Asian in 404 of 16297 chromosomes (freq: 0.02479), Other in 16 of 4579 chromosomes (freq: 0.003494), Ashkenazi Jewish in 22 of 6922 chromosomes (freq: 0.003178), European (non-Finnish) in 189 of 71137 chromosomes (freq: 0.002657), Latino in 46 of 25450 chromosomes (freq: 0.001807), African in 5 of 14750 chromosomes (freq: 0.000339), East Asian in 1 of 12487 chromosomes (freq: 0.00008), and European (Finnish) in 1 of 15186 chromosomes (freq: 0.000066). Chakrabarty et al. identified the variant p.Pro392Ser as a somatic driver mutation in tissue samples of 18 long-standing ulcerative colitis (UC) subjects at high risk of colorectal carcinoma. (Chakrabarty_2017_28524162). The p.Pro392Ser residue is not conserved in mammals and four out of five computational analyses (PolyPhen-2, SIFT, AlignGVGD, and MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. References: Chakrabarty, Sanjiban, et al. "Targeted sequencing-based analyses of candidate gene variants in ulcerative colitis-associated colorectal neoplasia." British journal of cancer 117.1 (2017): 136. Kalfa, Nicolas, et al. "Minor hypospadias: the “tip of the iceberg” of the partial androgen insensitivity syndrome." PloS one 8.4 (2013): e61824. | |
Laboratory of Diagnostic Genome Analysis, |
RCV001269900 | SCV001799543 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV001269900 | SCV001972056 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV001269900 | SCV001978058 | likely benign | not provided | no assertion criteria provided | clinical testing |