14-100734308-T-A

Variant names:

• chr14-100734308-T-A
• rs1802710
• NM_003836.7:c.564T>A

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003836.7(DLK1):​c.564T>A​(p.Ile188Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I188I) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DLK1 NM_003836.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.449

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=-0.449 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLK1	NM_003836.7	c.564T>A	p.Ile188Ile	synonymous_variant	Exon 5 of 5	ENST00000341267.9	NP_003827.4
DLK1	NM_001317172.2	c.564T>A	p.Ile188Ile	synonymous_variant	Exon 5 of 6		NP_001304101.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLK1	ENST00000341267.9	c.564T>A	p.Ile188Ile	synonymous_variant	Exon 5 of 5	1	NM_003836.7	ENSP00000340292.4
DLK1	ENST00000331224.10	c.564T>A	p.Ile188Ile	synonymous_variant	Exon 5 of 6	1		ENSP00000331081.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 94

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	2.8
DANN	Benign	0.84
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

Other links and lift over

dbSNP: rs1802710; hg19: chr14-101200645;