rs1800497

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_178510.2(ANKK1):c.2137G>A(p.Glu713Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 1,612,642 control chromosomes in the GnomAD database, including 43,632 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5539 hom., cov: 34)

Exomes 𝑓: 0.22 ( 38093 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.438

Variant links:

Genes affected

ANKK1 (HGNC:21027): (ankyrin repeat and kinase domain containing 1) The protein encoded by this gene belongs to the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways. This gene is closely linked to DRD2 gene (GeneID:1813) on chr 11, and a well studied restriction fragment length polymorphism (RFLP) designated TaqIA, was originally associated with the DRD2 gene, however, later was determined to be located in exon 8 of ANKK1 gene (PMIDs: 18621654, 15146457), where it causes a nonconservative amino acid substitution. It is not clear if this gene plays any role in neuropsychiatric disorders previously associated with Taq1A RFLP. [provided by RefSeq, Sep 2009]

ANKK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.9350004E-4).

BP6

Variant 11-113400106-G-A is Benign according to our data. Variant chr11-113400106-G-A is described in ClinVar as [Benign]. Clinvar id is 2105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANKK1	NM_178510.2 link	c.2137G>A	p.Glu713Lys	missense_variant	Exon 8 of 8	ENST00000303941.4	NP_848605.1	Q8NFD2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4 link	c.2137G>A	p.Glu713Lys	missense_variant	Exon 8 of 8	1	NM_178510.2	ENSP00000306678.3		Q8NFD2

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39295

AN:

152052

Hom.:

5529

Cov.:

show subpopulations

Gnomad AFR

AF:

0.341

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.318

Gnomad ASJ

AF:

0.169

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.290

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.195

Gnomad OTH

AF:

0.246

GnomAD2 exomes

AF:

0.264

AC:

65225

AN:

246888

AF XY:

0.254

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.449

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.400

Gnomad FIN exome

AF:

0.206

Gnomad NFE exome

AF:

0.192

Gnomad OTH exome

AF:

0.223

GnomAD4 exome

AF:

0.219

AC:

320284

AN:

1460472

Hom.:

38093

Cov.:

AF XY:

0.219

AC XY:

159389

AN XY:

726500

show subpopulations

Gnomad4 AFR exome

AF:

0.340

AC:

11392

AN:

33476

Gnomad4 AMR exome

AF:

0.428

AC:

19068

AN:

44564

Gnomad4 ASJ exome

AF:

0.148

AC:

3871

AN:

26118

Gnomad4 EAS exome

AF:

0.384

AC:

15248

AN:

39664

Gnomad4 SAS exome

AF:

0.283

AC:

24378

AN:

86172

Gnomad4 FIN exome

AF:

0.204

AC:

10806

AN:

52842

Gnomad4 NFE exome

AF:

0.199

AC:

221318

AN:

1111534

Gnomad4 Remaining exome

AF:

0.221

AC:

13326

AN:

60338

Heterozygous variant carriers

17023

34045

51068

68090

85113

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

8082

16164

24246

32328

40410

<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:

0.259

AC:

39345

AN:

152170

Hom.:

5539

Cov.:

AF XY:

0.262

AC XY:

19479

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.341

AC:

0.340824

AN:

0.340824

Gnomad4 AMR

AF:

0.319

AC:

0.318645

AN:

0.318645

Gnomad4 ASJ

AF:

0.169

AC:

0.168876

AN:

0.168876

Gnomad4 EAS

AF:

0.399

AC:

0.398874

AN:

0.398874

Gnomad4 SAS

AF:

0.291

AC:

0.291286

AN:

0.291286

Gnomad4 FIN

AF:

0.216

AC:

0.215808

AN:

0.215808

Gnomad4 NFE

AF:

0.195

AC:

0.195473

AN:

0.195473

Gnomad4 OTH

AF:

0.246

AC:

0.246452

AN:

0.246452

Heterozygous variant carriers

1502

3004

4506

6008

7510

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.216

Hom.:

8313

Bravo

AF:

0.273

TwinsUK

AF:

0.195

AC:

723

ALSPAC

AF:

0.186

AC:

718

ESP6500AA

AF:

0.327

AC:

1351

ESP6500EA

AF:

0.190

AC:

1598

ExAC

AF:

0.256

AC:

31010

Asia WGS

AF:

0.347

AC:

1207

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Apr 16, 2013

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

ANKK1-related disorder

Benign:1

Jul 22, 2021

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Schizophrenia

Benign:1

Center for Forensic Mental Health, Chiba University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:case-control

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Taq1A POLYMORPHISM

Benign:1

Oct 17, 2008

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.58

CADD

Benign

6.7

DANN

Benign

0.17

DEOGEN2

Benign

0.0055

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.026

LIST_S2

Benign

0.22

MetaRNN

Benign

0.00069

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.93

PrimateAI

Benign

0.31

PROVEAN

Benign

0.86

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.056

MPC

0.066

ClinPred

0.0026

GERP RS

2.0

Varity_R

0.038

gMVP

0.12

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over