rs62636615

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.85

Publications

5 publications found

Variant links:

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]

ULK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 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 VariationId is 718298.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 16 AR gene

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.2642G>A	p.Arg881Gln	missense splice_region	Exon 24 of 27	NP_055498.3
	ULK2	NM_001142610.2		c.2642G>A	p.Arg881Gln	missense splice_region	Exon 24 of 28	NP_001136082.1	Q8IYT8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ULK2	ENST00000395544.9	TSL:1 MANE Select	c.2642G>A	p.Arg881Gln	missense splice_region	Exon 24 of 27	ENSP00000378914.4	Q8IYT8
ULK2	ENST00000361658.6	TSL:1	c.2642G>A	p.Arg881Gln	missense splice_region	Exon 24 of 28	ENSP00000354877.2	Q8IYT8
ULK2	ENST00000945214.1		c.2642G>A	p.Arg881Gln	missense splice_region	Exon 24 of 27	ENSP00000615273.1

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1054

AN:

152154

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00197

AC:

491

AN:

249050

AF XY:

0.00154

show subpopulations

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 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.:

Cov.:

AF XY:

0.00101

AC XY:

733

AN XY:

726910

show subpopulations

African (AFR)

AF:

0.0264

AC:

882

AN:

33472

American (AMR)

AF:

0.00201

AC:

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26124

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86180

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53274

Middle Eastern (MID)

AF:

0.00296

AC:

AN:

5744

European-Non Finnish (NFE)

AF:

0.000465

AC:

517

AN:

1111770

Other (OTH)

AF:

0.00212

AC:

128

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

165

247

330

412

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00693

AC:

1056

AN:

152272

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0229

AC:

951

AN:

41546

American (AMR)

AF:

0.00392

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68018

Other (OTH)

AF:

0.00521

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

103

155

206

258

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00292

Hom.:

Bravo

AF:

0.00759

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0204

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00223

AC:

271

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000713

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.0058

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

PhyloP100

3.8

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.45

REVEL

Benign

0.064

Sift

Benign

0.36

Sift4G

Benign

0.34

Polyphen

0.0040

Vest4

0.11

MVP

0.45

MPC

0.16

ClinPred

0.019

GERP RS

3.4

Varity_R

0.059

gMVP

0.11

Mutation Taster

=82/18

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over