ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.575C>T (p.Ala192Val)

gnomAD frequency: 0.00023  dbSNP: rs62621089
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000757174 SCV000293761 likely benign not provided 2024-05-29 criteria provided, single submitter clinical testing See Variant Classification Assertion Criteria.
Illumina Laboratory Services, Illumina RCV001086953 SCV000410259 benign Hereditary sensory neuropathy-deafness-dementia syndrome 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 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757174 SCV000885309 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing The DNMT1 c.575C>T; p.Ala192Val variant (rs62621089, ClinVar variant ID 246280), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 0.2% (identified on 67 out of 30,782 chromosomes). The alanine at position 192 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Ala192Val variant on protein structure and function make conflicting predictions (SIFT: damaging, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ala192Val variant cannot be determined with certainty.
Labcorp Genetics (formerly Invitae), Labcorp RCV001086953 SCV001020732 likely benign Hereditary sensory neuropathy-deafness-dementia syndrome 2024-01-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002347928 SCV002644224 likely benign Inborn genetic diseases 2022-12-19 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.
CeGaT Center for Human Genetics Tuebingen RCV000757174 SCV004139493 benign not provided 2022-04-01 criteria provided, single submitter clinical testing DNMT1: BS1, BS2

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.