Submissions for variant NM_152383.5(DIS3L2):c.1680G>A (p.Leu560=)

gnomAD frequency: 0.00008  dbSNP: rs377644356

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000329100	SCV000428374	uncertain significance	Perlman syndrome	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000329100	SCV000561862	benign	Perlman syndrome	2023-12-07	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000329100	SCV002532399	uncertain significance	Perlman syndrome	2021-06-03	criteria provided, single submitter	curation
PreventionGenetics, part of Exact Sciences	RCV003950156	SCV004766324	likely benign	DIS3L2-related disorder	2019-12-11	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).