Submissions for variant NM_001130823.3(DNMT1):c.2914G>A (p.Val972Met)

gnomAD frequency: 0.00009  dbSNP: rs148038464

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000427007	SCV000510819	uncertain significance	not provided	2016-09-13	criteria provided, single submitter	clinical testing	Converted during submission to Uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000695923	SCV000824462	likely benign	Hereditary sensory neuropathy-deafness-dementia syndrome	2023-11-11	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000695923	SCV001286613	benign	Hereditary sensory neuropathy-deafness-dementia syndrome	2018-03-06	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV002436243	SCV002747035	likely benign	Inborn genetic diseases	2020-04-13	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003392234	SCV004120119	uncertain significance	DNMT1-related disorder	2023-09-13	criteria provided, single submitter	clinical testing	The DNMT1 c.2914G>A variant is predicted to result in the amino acid substitution p.Val972Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/19-10254644-C-T), which may be too common to be an undocumented cause of disease. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.