Submissions for variant NM_006892.4(DNMT3B):c.684C>T (p.Leu228=)

gnomAD frequency: 0.00003  dbSNP: rs373811098

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001138229	SCV001298266	uncertain significance	Immunodeficiency-centromeric instability-facial anomalies syndrome 1	2018-01-12	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.
Invitae	RCV001422542	SCV001625096	likely benign	Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency	2023-12-09	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001818892	SCV002065041	likely benign	not specified	2017-09-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003432925	SCV004152593	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	DNMT3B: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003942886	SCV004764022	likely benign	DNMT3B-related condition	2024-01-11	criteria provided, single submitter	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).