17-19786069-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014683.4(ULK2):c.2119G>A(p.Gly707Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.29

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21005806).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2119G>A	p.Gly707Ser	missense_variant	21/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2119G>A	p.Gly707Ser	missense_variant	21/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.2119G>A	p.Gly707Ser	missense_variant	21/28	1		P1
ULK2	ENST00000575432.1	c.138-64G>A		intron_variant		3
ULK2	ENST00000571137.1	n.300-2164G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412200 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 702156

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.14e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jul 14, 2021

The c.2119G>A (p.G707S) alteration is located in exon 21 (coding exon 21) of the ULK2 gene. This alteration results from a G to A substitution at nucleotide position 2119, causing the glycine (G) at amino acid position 707 to be replaced by a serine (S). 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	0.077
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
Cadd	Uncertain	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.24	T;T
Eigen	Benign	0.085
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.17
Sift	Benign	0.088	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.19	B;B
Vest4		0.29
MutPred		0.23		Gain of glycosylation at G707 (P = 0.0012);Gain of glycosylation at G707 (P = 0.0012);
MVP		0.64
MPC		0.13
ClinPred		0.73	D
GERP RS		5.5
Varity_R		0.13
gMVP		0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr17-19689382;