Submissions for variant NM_152383.5(DIS3L2):c.1447C>G (p.Arg483Gly)

gnomAD frequency: 0.00073  dbSNP: rs186865544

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000233813	SCV000291492	benign	Perlman syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000233813	SCV000895425	uncertain significance	Perlman syndrome	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000233813	SCV001297723	uncertain significance	Perlman syndrome	2017-04-27	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
GeneDx	RCV001762549	SCV001989984	uncertain significance	not provided	2019-05-15	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 23613427, 22306653, 24909261, 30256826)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001762549	SCV002009754	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000233813	SCV002532394	uncertain significance	Perlman syndrome	2022-03-10	criteria provided, single submitter	curation
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV000233813	SCV002768431	uncertain significance	Perlman syndrome	2020-05-01	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as 3C-VUS. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0200 - Variant is predicted to result in a missense amino acid change from arginine to glycine (exon 13). (N) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (210 Heterozygous, 0 Homozygous). (P) 0309 - Multiple alternative amino acid changes at the same position has been observed in gnomAD (highest allele count: 3631 Heterozygous, 66 Homozygous). (N) 0502 - Missense variant with conflicting in silico predictions with low conservation. (N) 0600 - Variant is located in the RNB domain (NCBI conserved domain). (N) 0710 - Comparable variants have some previous evidence for being benign (ClinVar). (B) 0804 - Variant has previously been described as variant of uncertain significance in two independent cases with consistent phenotype (ClinVar). (N) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant in the literature. (N) 1208 - Inheritance information for this variant is not currently available. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign
Revvity Omics, Revvity	RCV000233813	SCV003834679	uncertain significance	Perlman syndrome	2022-05-12	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001762549	SCV004699188	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	DIS3L2: BP4
GenomeConnect - Invitae Patient Insights Network	RCV000233813	SCV004228653	not provided	Perlman syndrome		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 12-04-2017 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.
PreventionGenetics, part of Exact Sciences	RCV003919985	SCV004746201	likely benign	DIS3L2-related disorder	2022-03-18	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).