Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2_SupportingPM5PP3_ModeratePP5
The NM_022552(DNMT3A):c.2645G>T(p.Arg882Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152016 control chromosomes in the gnomAD Genomes database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R882G) has been classified as Pathogenic.
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
GnomAD3 genomes AF: 0.00000658AC: 1AN: 152016Hom.: 0Cov.: 32 GnomAD3 exomes AF: 0.00000398AC: 1AN: 251040Hom.: 0 AF XY: 0.00AC XY: 0AN XY: 135696 GnomAD4 exome AF: 0.00000274AC: 4AN: 1461316Hom.: 0 AF XY: 0.00000275AC XY: 2AN XY: 726942
Submissions by phenotype
Acute myeloid leukemia
|Pathogenic, no assertion criteria provided||literature only||Database of Curated Mutations (DoCM)||Oct 02, 2014||- -|
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