17-19781102-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_014683.4(ULK2):c.2642G>A(p.Arg881Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00167 in 1,613,556 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (16 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (19 hom.)
• Consequence: ULK2 NM_014683.4 missense, splice_region
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.85

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 Benign. Variant got -10 ACMG points.

• BP6: Variant 17-19781102-C-T is Benign according to our data. Variant chr17-19781102-C-T is described in ClinVar as [Benign]. Clinvar id is 718298.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00693 (1056/152272) while in subpopulation AFR AF= 0.0229 (951/41546). AF 95% confidence interval is 0.0217. There are 16 homozygotes in gnomad4. There are 519 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2642G>A	p.Arg881Gln	missense_variant, splice_region_variant	24/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2642G>A	p.Arg881Gln	missense_variant, splice_region_variant	24/27	1	NM_014683.4	P1
ULK2	ENST00000361658.6	c.2642G>A	p.Arg881Gln	missense_variant, splice_region_variant	24/28	1		P1
ULK2	ENST00000571454.2	n.546G>A		splice_region_variant, non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1054 AN: 152154 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00197 AC: 491 AN: 249050 Hom.: 7 AF XY: 0.00154 AC XY: 208 AN XY: 134706

Gnomad AFR exome AF: 0.0230

Gnomad AMR exome AF: 0.00194

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000657

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000393

Gnomad OTH exome AF: 0.000820

GnomAD4 exome AF: 0.00112 AC: 1641 AN: 1461284 Hom.: 19 Cov.: 31 AF XY: 0.00101 AC XY: 733 AN XY: 726910

Gnomad4 AFR exome AF: 0.0264

Gnomad4 AMR exome AF: 0.00201

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000465

Gnomad4 OTH exome AF: 0.00212

GnomAD4 genome AF: 0.00693 AC: 1056 AN: 152272 Hom.: 16 Cov.: 32 AF XY: 0.00697 AC XY: 519 AN XY: 74462

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000456

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00162 Hom.: 4

Bravo AF: 0.00759

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0204 AC: 90

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00223 AC: 271

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000713

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.72	D
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.14	N;N
MutationTaster	Benign	0.59	N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.45	N;N
REVEL	Benign	0.064
Sift	Benign	0.36	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.0040	B;B
Vest4		0.11
MVP		0.45
MPC		0.16
ClinPred		0.019	T
GERP RS		3.4
Varity_R		0.059
gMVP		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.45		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.45		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs62636615; hg19: chr17-19684415;