Variant rs2295660 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_003836.7(DLK1):c.699T>C(p.Cys233=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00502 in 1,612,072 control chromosomes in the GnomAD database, including 170 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.012 ( 27 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 143 hom. )

Consequence

DLK1
NM_003836.7 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.583

Variant links:

Genes affected

DLK1 (HGNC:2907): (delta like non-canonical Notch ligand 1) This gene encodes a transmembrane protein that contains multiple epidermal growth factor repeats that functions as a regulator of cell growth. The encoded protein is involved in the differentiation of several cell types including adipocytes. This gene is located in a region of chromosome 14 frequently showing unparental disomy, and is imprinted and expressed from the paternal allele. A single nucleotide variant in this gene is associated with child and adolescent obesity and shows polar overdominance, where heterozygotes carrying an active paternal allele express the phenotype, while mutant homozygotes are normal. [provided by RefSeq, Nov 2015]

DLK1 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=-0.64).

BP6

Variant 14-100734443-T-C is Benign according to our data. Variant chr14-100734443-T-C is described in ClinVar as [Benign]. Clinvar id is 3037935.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.583 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLK1	NM_003836.7 linkuse as main transcript	c.699T>C	p.Cys233=	synonymous_variant	5/5	ENST00000341267.9
DLK1	NM_001317172.2 linkuse as main transcript	c.684+15T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLK1	ENST00000341267.9 linkuse as main transcript	c.699T>C	p.Cys233=	synonymous_variant	5/5	1	NM_003836.7	P1	P80370-1
DLK1	ENST00000331224.10 linkuse as main transcript	c.684+15T>C		intron_variant		1			P80370-2

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1857

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0581

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.0227

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0108

AC:

2689

AN:

249398

Hom.:

AF XY:

0.00946

AC XY:

1279

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.0129

Gnomad ASJ exome

AF:

0.000200

Gnomad EAS exome

AF:

0.0617

Gnomad SAS exome

AF:

0.00213

Gnomad FIN exome

AF:

0.0204

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.00804

GnomAD4 exome

AF:

0.00427

AC:

6232

AN:

1459812

Hom.:

143

Cov.:

AF XY:

0.00413

AC XY:

2997

AN XY:

726054

show subpopulations

Gnomad4 AFR exome

AF:

0.0261

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0000766

Gnomad4 EAS exome

AF:

0.0667

Gnomad4 SAS exome

AF:

0.00232

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.000508

Gnomad4 OTH exome

AF:

0.00774

GnomAD4 genome

AF:

0.0122

AC:

1856

AN:

152260

Hom.:

Cov.:

AF XY:

0.0131

AC XY:

973

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0248

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0575

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.0227

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00313

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

DLK1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.72

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