Variant 17-19776365-C-G 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.3095G>C(p.Ser1032Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,453,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

ULK2
NM_014683.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.38

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=0.21432063).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ULK2	NM_014683.4 linkuse as main transcript	c.3095G>C	p.Ser1032Thr	missense_variant	27/27	ENST00000395544.9	NP_055498.3	Q8IYT8
ULK2	NM_001142610.2 linkuse as main transcript	c.3095G>C	p.Ser1032Thr	missense_variant	27/28		NP_001136082.1	Q8IYT8
ULK2	XM_017025425.3 linkuse as main transcript	c.3158G>C	p.Ser1053Thr	missense_variant	27/28		XP_016880914.1
ULK2	XM_047437147.1 linkuse as main transcript	c.3014G>C	p.Ser1005Thr	missense_variant	27/28		XP_047293103.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ULK2	ENST00000395544.9 linkuse as main transcript	c.3095G>C	p.Ser1032Thr	missense_variant	27/27	1	NM_014683.4	ENSP00000378914.4		Q8IYT8
ULK2	ENST00000361658.6 linkuse as main transcript	c.3095G>C	p.Ser1032Thr	missense_variant	27/28	1		ENSP00000354877.2		Q8IYT8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000211

AC:

AN:

237306

Hom.:

AF XY:

0.00

AC XY:

AN XY:

128008

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000225

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000172

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1453786

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jun 16, 2024

The c.3095G>C (p.S1032T) alteration is located in exon 27 (coding exon 27) of the ULK2 gene. This alteration results from a G to C substitution at nucleotide position 3095, causing the serine (S) at amino acid position 1032 to be replaced by a threonine (T). 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

0.076

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.12

Eigen_PC

Benign

0.042

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

.;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.90

L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.98

N;N

REVEL

Benign

0.096

Sift

Benign

0.071

T;T

Sift4G

Benign

0.81

T;T

Polyphen

0.17

B;B

Vest4

0.60

MutPred

0.20

Loss of disorder (P = 0.0909);Loss of disorder (P = 0.0909);

MVP

0.63

MPC

0.24

ClinPred

0.090

GERP RS

5.8

Varity_R

0.14

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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