17-19795642-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014683.4(ULK2):c.2081C>G(p.Thr694Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.52

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2081C>G	p.Thr694Arg	missense_variant	20/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2081C>G	p.Thr694Arg	missense_variant	20/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.2081C>G	p.Thr694Arg	missense_variant	20/28	1		P1
ULK2	ENST00000575432.1	c.119C>G	p.Thr40Arg	missense_variant	2/5	3
ULK2	ENST00000571137.1	n.279C>G		non_coding_transcript_exon_variant	2/4	4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.2081C>G (p.T694R) alteration is located in exon 20 (coding exon 20) of the ULK2 gene. This alteration results from a C to G substitution at nucleotide position 2081, causing the threonine (T) at amino acid position 694 to be replaced by an arginine (R). 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	0.15
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.59	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.52	T;T
Polyphen		0.84	P;P
Vest4		0.69
MutPred		0.21		Gain of solvent accessibility (P = 0.0137);Gain of solvent accessibility (P = 0.0137);
MVP		0.61
MPC		0.29
ClinPred		0.85	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.71

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-19698955;