Variant 19-2191212-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_032482.3(DOT1L):c.465C>T(p.Asp155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000744 in 1,613,910 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 4 hom., cov: 31)

Exomes 𝑓: 0.00043 ( 5 hom. )

Consequence

DOT1L
NM_032482.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.937

Variant links:

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]

DOT1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 19-2191212-C-T is Benign according to our data. Variant chr19-2191212-C-T is described in ClinVar as [Benign]. Clinvar id is 777359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.937 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOT1L	NM_032482.3 linkuse as main transcript	c.465C>T	p.Asp155=	synonymous_variant	5/28	ENST00000398665.8	NP_115871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOT1L	ENST00000398665.8 linkuse as main transcript	c.465C>T	p.Asp155=	synonymous_variant	5/28	1	NM_032482.3	ENSP00000381657	P2	Q8TEK3-2
DOT1L	ENST00000686010.1 linkuse as main transcript	c.465C>T	p.Asp155=	synonymous_variant	5/28			ENSP00000510335	A2
DOT1L	ENST00000452696.5 linkuse as main transcript	c.393C>T	p.Asp131=	synonymous_variant	5/8	3		ENSP00000404284
DOT1L	ENST00000478937.3 linkuse as main transcript	c.*336C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	3		ENSP00000484015

Frequencies

GnomAD3 genomes

AF:

0.00377

AC:

574

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000895

AC:

223

AN:

249090

Hom.:

AF XY:

0.000651

AC XY:

AN XY:

135172

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000426

AC:

623

AN:

1461708

Hom.:

Cov.:

AF XY:

0.000364

AC XY:

265

AN XY:

727152

show subpopulations

Gnomad4 AFR exome

AF:

0.0131

Gnomad4 AMR exome

AF:

0.000604

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000971

Gnomad4 OTH exome

AF:

0.000646

GnomAD4 genome

AF:

0.00380

AC:

578

AN:

152202

Hom.:

Cov.:

AF XY:

0.00356

AC XY:

265

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0130

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00218

Hom.:

Bravo

AF:

0.00464

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 28, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.0

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over