rs17794370

chr17-19794663-G-A

Variant summary

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

The NM_014683.4(ULK2):c.2101+959C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,366 control chromosomes in the GnomAD database, including 3,888 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 0.21 (3888 hom., cov: 31)
• Consequence: ULK2 NM_014683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2101+959C>T		intron_variant		ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2101+959C>T		intron_variant		1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.2101+959C>T		intron_variant		1		P1
ULK2	ENST00000575432.1	c.137+959C>T		intron_variant		3
ULK2	ENST00000571137.1	n.299+959C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31965 AN: 151248 Hom.: 3888 Cov.: 31

Gnomad AFR AF: 0.0802

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.192

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.211 AC: 31971 AN: 151366 Hom.: 3888 Cov.: 31 AF XY: 0.213 AC XY: 15747 AN XY: 73868

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.257

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.192

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.206

Alfa AF: 0.261 Hom.: 11308

Bravo AF: 0.206

Asia WGS AF: 0.196 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
Cadd	Benign	10
Dann	Benign	0.88

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: rs17794370; hg19: chr17-19697976;