rs157397

Positions:

• chr17-19826182-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014683.4(ULK2):​c.792A>G​(p.Ala264=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,460,748 control chromosomes in the GnomAD database, including 646,771 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 0.89 (61272 hom., cov: 29)
  • Exomes 𝑓: 0.94 (585499 hom.)
• Consequence: ULK2 NM_014683.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.792A>G	p.Ala264=	synonymous_variant	11/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.792A>G	p.Ala264=	synonymous_variant	11/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.792A>G	p.Ala264=	synonymous_variant	11/28	1		P1
ULK2	ENST00000571177.5	n.165A>G		non_coding_transcript_exon_variant	4/7	5
ULK2	ENST00000580130.5	n.5-1000A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.895 AC: 135314 AN: 151254 Hom.: 61239 Cov.: 29

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.912

GnomAD3 exomes AF: 0.907 AC: 181524 AN: 200216 Hom.: 83447 AF XY: 0.912 AC XY: 100166 AN XY: 109874

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 0.594

Gnomad SAS exome AF: 0.847

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.966

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.943 AC: 1235195 AN: 1309378 Hom.: 585499 Cov.: 27 AF XY: 0.943 AC XY: 611761 AN XY: 649070

Gnomad4 AFR exome AF: 0.770

Gnomad4 AMR exome AF: 0.881

Gnomad4 ASJ exome AF: 0.978

Gnomad4 EAS exome AF: 0.661

Gnomad4 SAS exome AF: 0.851

Gnomad4 FIN exome AF: 0.969

Gnomad4 NFE exome AF: 0.964

Gnomad4 OTH exome AF: 0.918

GnomAD4 genome AF: 0.894 AC: 135395 AN: 151370 Hom.: 61272 Cov.: 29 AF XY: 0.893 AC XY: 66102 AN XY: 73994

Gnomad4 AFR AF: 0.785

Gnomad4 AMR AF: 0.901

Gnomad4 ASJ AF: 0.978

Gnomad4 EAS AF: 0.612

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.967

Gnomad4 OTH AF: 0.911

Alfa AF: 0.941 Hom.: 44539

Bravo AF: 0.883

Asia WGS AF: 0.725 AC: 2496 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs157397; hg19: chr17-19729495; COSMIC: COSV100860677;