rs1800497

Positions:

chr11-113400106-G-A

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
ANKK1	NM_178510.2 linkuse as main transcript	c.2137G>A	p.Glu713Lys	missense_variant	8/8	ENST00000303941.4	NP_848605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANKK1	ENST00000303941.4 linkuse as main transcript	c.2137G>A	p.Glu713Lys	missense_variant	8/8	1	NM_178510.2	ENSP00000306678	P1

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

GnomAD3 exomes

AF:

0.264

AC:

65225

AN:

246888

Hom.:

9971

AF XY:

0.254

AC XY:

34091

AN XY:

134200

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 SAS exome

AF:

0.289

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

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.384

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.204

Gnomad4 NFE exome

AF:

0.199

Gnomad4 OTH exome

AF:

0.221

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

Gnomad4 AMR

AF:

0.319

Gnomad4 ASJ

AF:

0.169

Gnomad4 EAS

AF:

0.399

Gnomad4 SAS

AF:

0.291

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.195

Gnomad4 OTH

AF:

0.246

Alfa

AF:

0.207

Hom.:

5053

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

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Apr 16, 2013

- -

ANKK1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 22, 2021

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

Benign, criteria provided, single submitter

case-control

Center for Forensic Mental Health, Chiba University

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Taq1A POLYMORPHISM

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Oct 17, 2008

- -

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

MutationTaster

Benign

1.0

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

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