17-19839201-T-C

Variant names:

• chr17-19839201-T-C
• rs281357
• NM_014683.4:c.705-618A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	NM_014683.4	MANE Select	c.705-618A>G		intron	N/A	NP_055498.3
	ULK2	NM_001142610.2		c.705-618A>G		intron	N/A	NP_001136082.1	Q8IYT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	ENST00000395544.9	TSL:1 MANE Select	c.705-618A>G		intron	N/A	ENSP00000378914.4	Q8IYT8
	ULK2	ENST00000361658.6	TSL:1	c.705-618A>G		intron	N/A	ENSP00000354877.2	Q8IYT8
	ULK2	ENST00000945214.1		c.705-618A>G		intron	N/A	ENSP00000615273.1

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

African (AFR) AF: 0.938 AC: 38965 AN: 41532

American (AMR) AF: 0.780 AC: 11910 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.642 AC: 2228 AN: 3468

East Asian (EAS) AF: 0.933 AC: 4812 AN: 5158

South Asian (SAS) AF: 0.797 AC: 3843 AN: 4824

European-Finnish (FIN) AF: 0.666 AC: 7005 AN: 10524

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44757 AN: 67922

Other (OTH) AF: 0.740 AC: 1562 AN: 2112

Alfa AF: 0.704 Hom.: 33790

Bravo AF: 0.776

Asia WGS AF: 0.870 AC: 3025 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.8
DANN	Benign	0.87
PhyloP100		0.55
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs281357; hg19: chr17-19742514;