17-19783817-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_014683.4(ULK2):c.2340C>T(p.Ser780=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,602,896 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0052 (37 hom.)
• Consequence: ULK2 NM_014683.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 17-19783817-G-A is Benign according to our data. Variant chr17-19783817-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2647564.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2340C>T	p.Ser780=	synonymous_variant	22/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2340C>T	p.Ser780=	synonymous_variant	22/27	1	NM_014683.4	P1

Frequencies

GnomAD3 genomes AF: 0.00375 AC: 571 AN: 152244 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00348

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00672

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.00364 AC: 886 AN: 243398 Hom.: 3 AF XY: 0.00363 AC XY: 478 AN XY: 131676

Gnomad AFR exome AF: 0.000827

Gnomad AMR exome AF: 0.000843

Gnomad ASJ exome AF: 0.000201

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000799

Gnomad FIN exome AF: 0.00273

Gnomad NFE exome AF: 0.00660

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00516 AC: 7488 AN: 1450534 Hom.: 37 Cov.: 31 AF XY: 0.00498 AC XY: 3595 AN XY: 721246

Gnomad4 AFR exome AF: 0.000665

Gnomad4 AMR exome AF: 0.000808

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.0000511

Gnomad4 SAS exome AF: 0.000658

Gnomad4 FIN exome AF: 0.00336

Gnomad4 NFE exome AF: 0.00630

Gnomad4 OTH exome AF: 0.00365

GnomAD4 genome AF: 0.00374 AC: 570 AN: 152362 Hom.: 5 Cov.: 33 AF XY: 0.00350 AC XY: 261 AN XY: 74504

Gnomad4 AFR AF: 0.000962

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00348

Gnomad4 NFE AF: 0.00670

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00486 Hom.: 0

Bravo AF: 0.00326

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

ULK2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	7.8
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs56181782; hg19: chr17-19687130;