17-19783772-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_014683.4(ULK2):c.2385C>T(p.Tyr795=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,601,922 control chromosomes in the GnomAD database, including 233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.024 (122 hom., cov: 32)
  • Exomes 𝑓: 0.0034 (111 hom.)
• Consequence: ULK2 NM_014683.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.268

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 17-19783772-G-A is Benign according to our data. Variant chr17-19783772-G-A is described in ClinVar as [Benign]. Clinvar id is 777152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.268 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ULK2	NM_014683.4	c.2385C>T	p.Tyr795=	synonymous_variant	22/27	ENST00000395544.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ULK2	ENST00000395544.9	c.2385C>T	p.Tyr795=	synonymous_variant	22/27	1	NM_014683.4	P1

Frequencies

GnomAD3 genomes AF: 0.0235 AC: 3581 AN: 152182 Hom.: 119 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.00951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00910

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000985

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00757 AC: 1840 AN: 243112 Hom.: 49 AF XY: 0.00609 AC XY: 800 AN XY: 131458

Gnomad AFR exome AF: 0.0797

Gnomad AMR exome AF: 0.00510

Gnomad ASJ exome AF: 0.00952

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00728

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000949

Gnomad OTH exome AF: 0.00394

GnomAD4 exome AF: 0.00336 AC: 4867 AN: 1449622 Hom.: 111 Cov.: 31 AF XY: 0.00322 AC XY: 2319 AN XY: 720716

Gnomad4 AFR exome AF: 0.0768

Gnomad4 AMR exome AF: 0.00584

Gnomad4 ASJ exome AF: 0.00865

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.00668

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000633

Gnomad4 OTH exome AF: 0.00786

GnomAD4 genome AF: 0.0236 AC: 3598 AN: 152300 Hom.: 122 Cov.: 32 AF XY: 0.0239 AC XY: 1783 AN XY: 74484

Gnomad4 AFR AF: 0.0778

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.00951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000970

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0116 Hom.: 29

Bravo AF: 0.0268

Asia WGS AF: 0.0110 AC: 37 AN: 3478

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
BayesDel_noAF	Benign	-0.51
Cadd	Benign	3.2
Dann	Benign	0.52

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

Publications

LitVar

Other links and lift over

dbSNP: rs56296267; hg19: chr17-19687085;