rs3824420

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_015158.5(KANK1):c.2000G>A(p.Arg667His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0128 in 1,613,676 control chromosomes in the GnomAD database, including 1,241 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.027 ( 201 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1040 hom. )

Consequence

KANK1
NM_015158.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.70

Publications

17 publications found

Variant links:

Genes affected

KANK1 (HGNC:19309): (KN motif and ankyrin repeat domains 1) The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

KANK1 Gene-Disease associations (from GenCC):

spastic quadriplegic cerebral palsy
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
cerebral palsy, spastic quadriplegic, 2
Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

KANK1 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=0.0020582974).

BP6

Variant 9-712766-G-A is Benign according to our data. Variant chr9-712766-G-A is described in ClinVar as Benign. ClinVar VariationId is 1166350.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5 link	c.2000G>A	p.Arg667His	missense_variant	Exon 3 of 12	ENST00000382297.7	NP_055973.2	Q14678-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7 link	c.2000G>A	p.Arg667His	missense_variant	Exon 3 of 12	1	NM_015158.5	ENSP00000371734.2		Q14678-1

Frequencies

GnomAD3 genomes

AF:

0.0269

AC:

4088

AN:

152096

Hom.:

199

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0309

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0821

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.197

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0297

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00137

Gnomad OTH

AF:

0.0248

GnomAD2 exomes

AF:

0.0380

AC:

9513

AN:

250034

AF XY:

0.0324

show subpopulations

Gnomad AFR exome

AF:

0.0325

Gnomad AMR exome

AF:

0.123

Gnomad ASJ exome

AF:

0.00279

Gnomad EAS exome

AF:

0.196

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.0257

GnomAD4 exome

AF:

0.0113

AC:

16569

AN:

1461462

Hom.:

1040

Cov.:

AF XY:

0.0105

AC XY:

7633

AN XY:

726994

show subpopulations

African (AFR)

AF:

0.0289

AC:

968

AN:

33474

American (AMR)

AF:

0.118

AC:

5261

AN:

44588

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

26124

East Asian (EAS)

AF:

0.151

AC:

5982

AN:

39680

South Asian (SAS)

AF:

0.00860

AC:

741

AN:

86190

European-Finnish (FIN)

AF:

0.0259

AC:

1383

AN:

53400

Middle Eastern (MID)

AF:

0.00295

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000734

AC:

816

AN:

1111846

Other (OTH)

AF:

0.0222

AC:

1342

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1015

2031

3046

4062

5077

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

238

476

714

952

1190

<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:

0.0269

AC:

4088

AN:

152214

Hom.:

201

Cov.:

AF XY:

0.0303

AC XY:

2251

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.0308

AC:

1281

AN:

41528

American (AMR)

AF:

0.0825

AC:

1262

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.197

AC:

1016

AN:

5164

South Asian (SAS)

AF:

0.0122

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0297

AC:

315

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00137

AC:

AN:

68026

Other (OTH)

AF:

0.0241

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

187

373

560

746

933

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0136

Hom.:

326

Bravo

AF:

0.0333

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0331

AC:

146

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.0323

AC:

3919

Asia WGS

AF:

0.106

AC:

369

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 05, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 23263489) -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.0030

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.0096

T;T;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.075

LIST_S2

Benign

0.70

.;T;.;T

MetaRNN

Benign

0.0021

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.43

N;N;N;.

PhyloP100

-1.7

PrimateAI

Benign

0.17

PROVEAN

Benign

-0.16

N;.;N;N

REVEL

Benign

0.17

Sift

Benign

0.43

T;.;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0010

B;B;B;.

Vest4

0.039

ClinPred

0.0055

GERP RS

-12

Varity_R

0.015

gMVP

0.26

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over