rs193921089

chr17-19845333-C-A

Variant summary

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

The NM_014683.4(ULK2):c.514G>T(p.Ala172Ser) 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 (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 7.55

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.514G>T	p.Ala172Ser	missense_variant	7/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.514G>T	p.Ala172Ser	missense_variant	7/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.514G>T	p.Ala172Ser	missense_variant	7/28	1		P1
ULK2	ENST00000574732.6	c.*256G>T		3_prime_UTR_variant, NMD_transcript_variant	4/7	5
ULK2	ENST00000580118.2	c.*290G>T		3_prime_UTR_variant, NMD_transcript_variant	6/8	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

Malignant tumor of prostate Uncertain:1

Uncertain significance, no assertion criteria provided

literature only

Science for Life laboratory, Karolinska Institutet

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
Cadd	Pathogenic	27
Dann	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.70	D;D
MetaSVM	Benign	-0.36	T
MutationAssessor	Benign	-0.14	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0030	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.63
MutPred		0.37		Gain of glycosylation at A172 (P = 0.0545);Gain of glycosylation at A172 (P = 0.0545);
MVP		0.74
MPC		1.1
ClinPred		0.93	D
GERP RS		5.2
Varity_R		0.86
gMVP		0.38

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

Other links and lift over

dbSNP: rs193921089; hg19: chr17-19748646; COSMIC: COSV64444294; COSMIC: COSV64444294;