rs205096

Positions:

• chr17-19779014-G-A
• chr17-19779014-G-C
• chr17-19779014-G-T

Variant summary

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

The NM_014683.4(ULK2):​c.2917-1298C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,280 control chromosomes in the GnomAD database, including 68,081 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 0.94 (68081 hom., cov: 32)
• Consequence: ULK2 NM_014683.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2917-1298C>T		intron_variant		ENST00000395544.9
ULK2	NM_001142610.2	c.2917-1298C>T		intron_variant
ULK2	XM_017025425.3	c.2980-1298C>T		intron_variant
ULK2	XM_047437147.1	c.2836-1298C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2917-1298C>T		intron_variant		1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.2917-1298C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143707 AN: 152162 Hom.: 68031 Cov.: 32

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.983

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.968

Gnomad OTH AF: 0.950

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

GnomAD4 genome AF: 0.944 AC: 143816 AN: 152280 Hom.: 68081 Cov.: 32 AF XY: 0.942 AC XY: 70125 AN XY: 74454

Gnomad4 AFR AF: 0.934

Gnomad4 AMR AF: 0.929

Gnomad4 ASJ AF: 0.983

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.970

Gnomad4 NFE AF: 0.968

Gnomad4 OTH AF: 0.950

Alfa AF: 0.954 Hom.: 11647

Bravo AF: 0.943

Asia WGS AF: 0.794 AC: 2761 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.71
DANN	Benign	0.32

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: rs205096; hg19: chr17-19682327;