Variant 17-19781061-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_014683.4(ULK2):c.2683C>A(p.Leu895Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

ULK2
NM_014683.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.40

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 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.77

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK2	NM_014683.4 linkuse as main transcript	c.2683C>A	p.Leu895Ile	missense_variant	24/27	ENST00000395544.9	NP_055498.3	Q8IYT8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ULK2	ENST00000395544.9 linkuse as main transcript	c.2683C>A	p.Leu895Ile	missense_variant	24/27	1	NM_014683.4	ENSP00000378914.4	Q8IYT8
ULK2	ENST00000361658.6 linkuse as main transcript	c.2683C>A	p.Leu895Ile	missense_variant	24/28	1		ENSP00000354877.2	Q8IYT8
ULK2	ENST00000571454.2 linkuse as main transcript	n.*25C>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74280

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Feb 16, 2023

The c.2683C>A (p.L895I) alteration is located in exon 24 (coding exon 24) of the ULK2 gene. This alteration results from a C to A substitution at nucleotide position 2683, causing the leucine (L) at amino acid position 895 to be replaced by an isoleucine (I). 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

Uncertain

0.49

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

T;T

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

.;D

M_CAP

Benign

0.063

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Uncertain

-0.040

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-1.8

N;N

REVEL

Uncertain

0.44

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0060

D;D

Polyphen

1.0

D;D

Vest4

0.66

MVP

0.76

MPC

0.52

ClinPred

0.95

GERP RS

3.5

Varity_R

0.29

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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