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rs1800497

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. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5539 hom., cov: 34)
Exomes 𝑓: 0.22 ( 38093 hom. )

Consequence

ANKK1
NM_178510.2 missense

Scores

18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

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]

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 [Likely_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 UniProt
ANKK1NM_178510.2 linkuse as main transcriptc.2137G>A p.Glu713Lys missense_variant 8/8 ENST00000303941.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ANKK1ENST00000303941.4 linkuse as main transcriptc.2137G>A p.Glu713Lys missense_variant 8/81 NM_178510.2 P1

Frequencies

GnomAD3 genomes
AF:
0.258
AC:
39295
AN:
152052
Hom.:
5529
Cov.:
34
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.:
41
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.:
34
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/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Apr 16, 2013- -
Schizophrenia Benign:1
Benign, criteria provided, single submittercase-controlCenter for Forensic Mental Health, Chiba University-- -
Taq1A POLYMORPHISM Benign:1
Benign, no assertion criteria providedliterature onlyOMIMOct 17, 2008- -
ANKK1-related condition Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 22, 2021This 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). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.053
BayesDel_addAF
Benign
-0.66
T
BayesDel_noAF
Benign
-0.58
Cadd
Benign
6.7
Dann
Benign
0.17
DEOGEN2
Benign
0.0055
T
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.026
N
LIST_S2
Benign
0.22
T
MetaRNN
Benign
0.00069
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.93
L
MutationTaster
Benign
1.0
P
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.86
N
REVEL
Benign
0.059
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.056
MPC
0.066
ClinPred
0.0026
T
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.

Other links and lift over

dbSNP: rs1800497; hg19: chr11-113270828; COSMIC: COSV58272178; COSMIC: COSV58272178; API