Submissions for variant NM_006892.4(DNMT3B):c.2142G>A (p.Leu714=)

gnomAD frequency: 0.00045  dbSNP: rs143847495

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000636696	SCV000758136	likely benign	Centromeric instability of chromosomes 1,9 and 16 and immunodeficiency	2025-02-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001141327	SCV001301665	uncertain significance	Immunodeficiency-centromeric instability-facial anomalies syndrome 1	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.
CeGaT Center for Human Genetics Tuebingen	RCV001702700	SCV002496667	likely benign	not provided	2024-09-01	criteria provided, single submitter	clinical testing	DNMT3B: BP4, BP7
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001702700	SCV005876082	likely benign	not provided	2024-01-18	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001702700	SCV001931771	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001702700	SCV001967538	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937912	SCV004754233	likely benign	DNMT3B-related disorder	2021-03-09	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).