17-19826182-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_014683.4(ULK2):​c.792A>T​(p.Ala264Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,311,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 29)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ULK2 NM_014683.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP7: Synonymous conserved (PhyloP=-1.84 with no splicing effect.

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>T	p.Ala264Ala	synonymous	Exon 11 of 27	NP_055498.3
	ULK2	NM_001142610.2		c.792A>T	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>T	p.Ala264Ala	synonymous	Exon 11 of 27	ENSP00000378914.4
	ULK2	ENST00000361658.6	TSL:1	c.792A>T	p.Ala264Ala	synonymous	Exon 11 of 28	ENSP00000354877.2
	ULK2	ENST00000571177.5	TSL:5	n.165A>T		non_coding_transcript_exon	Exon 4 of 7

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1311082 Hom.: 0 Cov.: 27 AF XY: 0.00000154 AC XY: 1 AN XY: 649884

African (AFR) AF: 0.00 AC: 0 AN: 29108

American (AMR) AF: 0.00 AC: 0 AN: 31448

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22366

East Asian (EAS) AF: 0.00 AC: 0 AN: 34056

South Asian (SAS) AF: 0.00 AC: 0 AN: 60028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47026

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5246

European-Non Finnish (NFE) AF: 9.72e-7 AC: 1 AN: 1028708

Other (OTH) AF: 0.00 AC: 0 AN: 53096

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	2.4
DANN	Benign	0.67
PhyloP100		-1.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;