rs1060499754

Variant names:

• chr17-19797472-T-A
• rs1060499754
• NM_014683.4:c.1733A>T

Your query was ambiguous. Multiple possible variants found:

• chr17-19797472-T-A
• chr17-19797472-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2 PM5 BP4_Moderate

The NM_014683.4(ULK2):​c.1733A>T​(p.His578Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H578R) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.71

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
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr17-19797472-T-C is described in Lovd as [Pathogenic].
• BP4: Computational evidence support a benign effect (MetaRNN=0.19878003).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ULK2	NM_014683.4	c.1733A>T	p.His578Leu	missense_variant	Exon 18 of 27	ENST00000395544.9	NP_055498.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ULK2	ENST00000395544.9	c.1733A>T	p.His578Leu	missense_variant	Exon 18 of 27	1	NM_014683.4	ENSP00000378914.4
ULK2	ENST00000361658.6	c.1733A>T	p.His578Leu	missense_variant	Exon 18 of 28	1		ENSP00000354877.2
ULK2	ENST00000580130.5	n.*103A>T		downstream_gene_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.95
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.044
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.10
Sift	Benign	0.22	T;T
Sift4G	Benign	0.32	T;T
Polyphen		0.0020	B;B
Vest4		0.17
MutPred		0.20		Loss of glycosylation at S574 (P = 0.1039);Loss of glycosylation at S574 (P = 0.1039);
MVP		0.52
MPC		0.17
ClinPred		0.86	D
GERP RS		5.8
Varity_R		0.29
gMVP		0.55

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

LitVar

Other links and lift over

dbSNP: rs1060499754; hg19: chr17-19700785;