17-19839201-T-C

Position:

• chr17-19839201-T-C

Variant summary

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

The NM_014683.4(ULK2):​c.705-618A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.762 in 152,008 control chromosomes in the GnomAD database, including 45,407 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 0.76 (45407 hom., cov: 30)
• Consequence: ULK2 NM_014683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.547

Genes affected

ULK2 (HGNC:13480): (unc-51 like autophagy activating kinase 2) This gene encodes a protein that is similar to a serine/threonine kinase in C. elegans which is involved in axonal elongation. The structure of this protein is similar to the C. elegans protein in that both proteins have an N-terminal kinase domain, a central proline/serine rich (PS) domain, and a C-terminal (C) domain. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternatively spliced transcript variants encoding the same protein have been identified. [provided by RefSeq, Dec 2008]

ULK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK2	NM_014683.4	c.705-618A>G		intron_variant		ENST00000395544.9	NP_055498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK2	ENST00000395544.9	c.705-618A>G		intron_variant		1	NM_014683.4	ENSP00000378914.4
ULK2	ENST00000361658.6	c.705-618A>G		intron_variant		1		ENSP00000354877.2
ULK2	ENST00000571177.5	n.78-618A>G		intron_variant		5
ULK2	ENST00000574732.6	n.*447-618A>G		intron_variant		5		ENSP00000465666.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115721 AN: 151890 Hom.: 45337 Cov.: 30

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.933

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.666

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.737

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

GnomAD4 genome AF: 0.762 AC: 115847 AN: 152008 Hom.: 45407 Cov.: 30 AF XY: 0.766 AC XY: 56888 AN XY: 74266

Gnomad4 AFR AF: 0.938

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.797

Gnomad4 FIN AF: 0.666

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.740

Alfa AF: 0.705 Hom.: 23731

Bravo AF: 0.776

Asia WGS AF: 0.870 AC: 3025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.8
DANN	Benign	0.87

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: rs281357; hg19: chr17-19742514;