rs34647366

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_004523.4(KIF11):c.2512A>C(p.Asn838His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000614 in 1,607,626 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00070 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00061 ( 11 hom. )

Consequence

KIF11
NM_004523.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.72

Publications

3 publications found

Variant links:

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

KIF11 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P

KIF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047149956).

BP6

Variant 10-92645607-A-C is Benign according to our data. Variant chr10-92645607-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 435614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 106 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF11	NM_004523.4 link	c.2512A>C	p.Asn838His	missense_variant	Exon 18 of 22	ENST00000260731.5	NP_004514.2	P52732

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF11	ENST00000260731.5 link	c.2512A>C	p.Asn838His	missense_variant	Exon 18 of 22	1	NM_004523.4	ENSP00000260731.3		P52732

Frequencies

GnomAD3 genomes

AF:

0.000696

AC:

106

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.0205

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00136

AC:

333

AN:

244526

AF XY:

0.00119

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00223

Gnomad ASJ exome

AF:

0.0225

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.000605

AC:

881

AN:

1455308

Hom.:

Cov.:

AF XY:

0.000571

AC XY:

413

AN XY:

723314

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33130

American (AMR)

AF:

0.00225

AC:

AN:

43638

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

553

AN:

25936

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

84738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.000102

AC:

113

AN:

1109158

Other (OTH)

AF:

0.00195

AC:

117

AN:

60126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

118

157

196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152318

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.0000240

AC:

AN:

41584

American (AMR)

AF:

0.00124

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0205

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00134

Hom.:

Bravo

AF:

0.00107

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.00114

AC:

139

EpiCase

AF:

0.000383

EpiControl

AF:

0.000415

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 07, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Feb 22, 2017

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Inborn genetic diseases

Benign:1

Oct 18, 2021

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

KIF11-related disorder

Benign:1

Apr 18, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as 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

0.058

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.16

Eigen

Benign

-0.22

Eigen_PC

Benign

0.013

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.52

M_CAP

Benign

0.013

MetaRNN

Benign

0.0047

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.7

PhyloP100

2.7

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.91

REVEL

Benign

0.12

Sift

Benign

0.35

Sift4G

Benign

0.17

Polyphen

0.0

Vest4

0.14

MVP

0.58

MPC

0.30

ClinPred

0.034

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.073

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(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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rs34647366

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