Variant 17-19796123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014683.4(ULK2):c.1969G>A(p.Glu657Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,613,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 1 hom. )

Consequence

ULK2
NM_014683.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.14

Variant links:

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]

ULK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13101101).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4 linkuse as main transcript	c.1969G>A	p.Glu657Lys	missense_variant	19/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
ULK2	ENST00000395544.9 linkuse as main transcript	c.1969G>A	p.Glu657Lys	missense_variant	19/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6 linkuse as main transcript	c.1969G>A	p.Glu657Lys	missense_variant	19/28	1		P1
ULK2	ENST00000575432.1 linkuse as main transcript	c.7G>A	p.Glu3Lys	missense_variant	1/5	3
ULK2	ENST00000571137.1 linkuse as main transcript	n.167G>A		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000560

AC:

AN:

250220

Hom.:

AF XY:

0.0000740

AC XY:

AN XY:

135224

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000226

AC:

AN:

1461030

Hom.:

Cov.:

AF XY:

0.0000344

AC XY:

AN XY:

726796

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000671

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000576

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.1969G>A (p.E657K) alteration is located in exon 19 (coding exon 19) of the ULK2 gene. This alteration results from a G to A substitution at nucleotide position 1969, causing the glutamic acid (E) at amino acid position 657 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.37

Cadd

Benign

Dann

Benign

0.77

DEOGEN2

Benign

0.11

T;T

Eigen

Benign

-0.020

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.0095

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.56

D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

-0.84

N;N

REVEL

Benign

0.15

Sift

Benign

0.89

T;T

Sift4G

Benign

0.90

T;T

Polyphen

0.51

P;P

Vest4

0.36

MVP

0.61

MPC

0.15

ClinPred

0.035

GERP RS

6.0

Varity_R

0.13

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over