17-19783852-C-T

Variant names:

• chr17-19783852-C-T
• rs142816411
• NM_014683.4:c.2305G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014683.4(ULK2):​c.2305G>A​(p.Val769Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000447 in 1,588,188 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. V769L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: ULK2 NM_014683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060535222).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014683.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	NM_014683.4	MANE Select	c.2305G>A	p.Val769Met	missense	Exon 22 of 27	NP_055498.3
	ULK2	NM_001142610.2		c.2305G>A	p.Val769Met	missense	Exon 22 of 28	NP_001136082.1	Q8IYT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	ENST00000395544.9	TSL:1 MANE Select	c.2305G>A	p.Val769Met	missense	Exon 22 of 27	ENSP00000378914.4	Q8IYT8
	ULK2	ENST00000361658.6	TSL:1	c.2305G>A	p.Val769Met	missense	Exon 22 of 28	ENSP00000354877.2	Q8IYT8
	ULK2	ENST00000945214.1		c.2305G>A	p.Val769Met	missense	Exon 22 of 27	ENSP00000615273.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152242 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000260 AC: 6 AN: 230586 AF XY: 0.0000160

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000102

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000460 AC: 66 AN: 1435946 Hom.: 0 Cov.: 30 AF XY: 0.0000518 AC XY: 37 AN XY: 713656

African (AFR) AF: 0.0000309 AC: 1 AN: 32330

American (AMR) AF: 0.000123 AC: 5 AN: 40744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25392

East Asian (EAS) AF: 0.0000518 AC: 2 AN: 38612

South Asian (SAS) AF: 0.0000369 AC: 3 AN: 81226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5196

European-Non Finnish (NFE) AF: 0.0000482 AC: 53 AN: 1100078

Other (OTH) AF: 0.0000337 AC: 2 AN: 59390

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152242 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74372

African (AFR) AF: 0.0000241 AC: 1 AN: 41458

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000416

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ExAC AF: 0.0000330 AC: 4

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	2.9
DANN	Benign	0.61
DEOGEN2	Benign	0.089	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.0
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.42	N
REVEL	Benign	0.043
Sift	Benign	0.36	T
Sift4G	Benign	0.39	T
Polyphen		0.0020	B
Vest4		0.32
MutPred		0.11		Gain of glycosylation at P772 (P = 0.1592)
MVP		0.48
MPC		0.13
ClinPred		0.031	T
GERP RS		-0.93
Varity_R		0.032
gMVP		0.50
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs142816411; hg19: chr17-19687165; COSMIC: COSV100860741;