rs2269879

Positions:

• chr19-2194897-T-C
• chr19-2194897-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032482.3(DOT1L):​c.651+320T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,144 control chromosomes in the GnomAD database, including 54,620 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.84 (54620 hom., cov: 32)
• Consequence: DOT1L NM_032482.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.46

Genes affected

DOT1L (HGNC:24948): (DOT1 like histone lysine methyltransferase) The protein encoded by this gene is a histone methyltransferase that methylates lysine-79 of histone H3. It is inactive against free core histones, but shows significant histone methyltransferase activity against nucleosomes. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOT1L	NM_032482.3	c.651+320T>C		intron_variant		ENST00000398665.8	NP_115871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOT1L	ENST00000398665.8	c.651+320T>C		intron_variant		1	NM_032482.3	ENSP00000381657	P2
DOT1L	ENST00000452696.5	c.579+320T>C		intron_variant		3		ENSP00000404284
DOT1L	ENST00000686010.1	c.651+320T>C		intron_variant				ENSP00000510335	A2

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127915 AN: 152026 Hom.: 54597 Cov.: 32

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.930

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.915

Gnomad OTH AF: 0.866

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.841 AC: 127988 AN: 152144 Hom.: 54620 Cov.: 32 AF XY: 0.844 AC XY: 62747 AN XY: 74386

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.815

Gnomad4 ASJ AF: 0.915

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.930

Gnomad4 NFE AF: 0.915

Gnomad4 OTH AF: 0.858

Alfa AF: 0.901 Hom.: 89207

Bravo AF: 0.825

Asia WGS AF: 0.786 AC: 2737 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.17
DANN	Benign	0.21
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2269879; hg19: chr19-2194896;