NM_014683.4:c.792A>G

Variant names:

• chr17-19826182-T-C
• rs157397
• NM_014683.4:c.792A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_014683.4(ULK2):​c.792A>G​(p.Ala264Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,460,748 control chromosomes in the GnomAD database, including 646,771 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (61272 hom., cov: 29)
  • Exomes 𝑓: 0.94 (585499 hom.)
• Consequence: ULK2 NM_014683.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 16 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	NM_014683.4	MANE Select	c.792A>G	p.Ala264Ala	synonymous	Exon 11 of 27	NP_055498.3
	ULK2	NM_001142610.2		c.792A>G	p.Ala264Ala	synonymous	Exon 11 of 28	NP_001136082.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ULK2	ENST00000395544.9	TSL:1 MANE Select	c.792A>G	p.Ala264Ala	synonymous	Exon 11 of 27	ENSP00000378914.4
	ULK2	ENST00000361658.6	TSL:1	c.792A>G	p.Ala264Ala	synonymous	Exon 11 of 28	ENSP00000354877.2
	ULK2	ENST00000571177.5	TSL:5	n.165A>G		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes AF: 0.895 AC: 135314 AN: 151254 Hom.: 61239 Cov.: 29

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.901

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.612

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.967

Gnomad OTH AF: 0.912

GnomAD2 exomes AF: 0.907 AC: 181524 AN: 200216 AF XY: 0.912

Gnomad AFR exome AF: 0.769

Gnomad AMR exome AF: 0.877

Gnomad ASJ exome AF: 0.979

Gnomad EAS exome AF: 0.594

Gnomad FIN exome AF: 0.970

Gnomad NFE exome AF: 0.966

Gnomad OTH exome AF: 0.934

GnomAD4 exome AF: 0.943 AC: 1235195 AN: 1309378 Hom.: 585499 Cov.: 27 AF XY: 0.943 AC XY: 611761 AN XY: 649070

African (AFR) AF: 0.770 AC: 22281 AN: 28930

American (AMR) AF: 0.881 AC: 27642 AN: 31366

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 21870 AN: 22360

East Asian (EAS) AF: 0.661 AC: 22410 AN: 33894

South Asian (SAS) AF: 0.851 AC: 50943 AN: 59882

European-Finnish (FIN) AF: 0.969 AC: 45522 AN: 46996

Middle Eastern (MID) AF: 0.958 AC: 5024 AN: 5242

European-Non Finnish (NFE) AF: 0.964 AC: 990855 AN: 1027712

Other (OTH) AF: 0.918 AC: 48648 AN: 52996

GnomAD4 genome AF: 0.894 AC: 135395 AN: 151370 Hom.: 61272 Cov.: 29 AF XY: 0.893 AC XY: 66102 AN XY: 73994

African (AFR) AF: 0.785 AC: 32488 AN: 41376

American (AMR) AF: 0.901 AC: 13712 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3388 AN: 3464

East Asian (EAS) AF: 0.612 AC: 3149 AN: 5144

South Asian (SAS) AF: 0.840 AC: 4032 AN: 4800

European-Finnish (FIN) AF: 0.970 AC: 9946 AN: 10252

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.967 AC: 65581 AN: 67812

Other (OTH) AF: 0.911 AC: 1912 AN: 2098

Alfa AF: 0.939 Hom.: 49803

Bravo AF: 0.883

Asia WGS AF: 0.725 AC: 2496 AN: 3442

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.5
DANN	Benign	0.66
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs157397; hg19: chr17-19729495; COSMIC: COSV100860677;