NM_014683.4:c.2385C>T

Variant names:

• chr17-19783772-G-A
• rs56296267
• NM_014683.4:c.2385C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_014683.4(ULK2):​c.2385C>T​(p.Tyr795Tyr) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.268
• Publications: 2 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 -21 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 VariationId is 777152.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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.

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.2385C>T	p.Tyr795Tyr	synonymous	Exon 22 of 27	NP_055498.3
	ULK2	NM_001142610.2		c.2385C>T	p.Tyr795Tyr	synonymous	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.2385C>T	p.Tyr795Tyr	synonymous	Exon 22 of 27	ENSP00000378914.4	Q8IYT8
	ULK2	ENST00000361658.6	TSL:1	c.2385C>T	p.Tyr795Tyr	synonymous	Exon 22 of 28	ENSP00000354877.2	Q8IYT8
	ULK2	ENST00000945214.1		c.2385C>T	p.Tyr795Tyr	synonymous	Exon 22 of 27	ENSP00000615273.1

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

GnomAD2 exomes AF: 0.00757 AC: 1840 AN: 243112 AF XY: 0.00609

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 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

African (AFR) AF: 0.0768 AC: 2532 AN: 32976

American (AMR) AF: 0.00584 AC: 252 AN: 43132

Ashkenazi Jewish (ASJ) AF: 0.00865 AC: 225 AN: 26004

East Asian (EAS) AF: 0.0000256 AC: 1 AN: 39064

South Asian (SAS) AF: 0.00668 AC: 558 AN: 83544

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53316

Middle Eastern (MID) AF: 0.0221 AC: 127 AN: 5734

European-Non Finnish (NFE) AF: 0.000633 AC: 700 AN: 1105902

Other (OTH) AF: 0.00786 AC: 471 AN: 59950

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

African (AFR) AF: 0.0778 AC: 3233 AN: 41550

American (AMR) AF: 0.0111 AC: 170 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00951 AC: 33 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00911 AC: 44 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.000970 AC: 66 AN: 68026

Other (OTH) AF: 0.0213 AC: 45 AN: 2112

Alfa AF: 0.0119 Hom.: 38

Bravo AF: 0.0268

Asia WGS AF: 0.0110 AC: 37 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.2
DANN	Benign	0.52
PhyloP100		0.27
Mutation Taster		=100/0	polymorphism (auto)

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: rs56296267; hg19: chr17-19687085;