19-2213632-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_032482.3(DOT1L):c.1651T>G(p.Leu551Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,400 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032482.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOT1L | NM_032482.3 | c.1651T>G | p.Leu551Val | missense_variant | 17/28 | ENST00000398665.8 | |
LOC124904611 | XR_007067087.1 | n.1135A>C | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOT1L | ENST00000398665.8 | c.1651T>G | p.Leu551Val | missense_variant | 17/28 | 1 | NM_032482.3 | P2 | |
ENST00000585593.1 | n.1135A>C | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 151978Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461422Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726994
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 151978Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74216
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2022 | The c.1651T>G (p.L551V) alteration is located in exon 17 (coding exon 17) of the DOT1L gene. This alteration results from a T to G substitution at nucleotide position 1651, causing the leucine (L) at amino acid position 551 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at