Genetic Variant KIF2B:p.Arg257Cys (chr17-53823802-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_032559.5(KIF2B):c.769C>T(p.Arg257Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000933 in 1,614,224 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 13 hom. )

Consequence

KIF2B
NM_032559.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0990

Variant links:

Genes affected

KIF2B (HGNC:29443): (kinesin family member 2B) Predicted to enable microtubule binding activity and microtubule motor activity. Involved in metaphase plate congression; microtubule depolymerization; and regulation of chromosome segregation. Located in intercellular bridge; mitotic spindle; and nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

KIF2B links:

ENSG00000285939 (HGNC:):

ENSG00000285939 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010803491).

BP6

Variant 17-53823802-C-T is Benign according to our data. Variant chr17-53823802-C-T is described in ClinVar as [Benign]. Clinvar id is 789094.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 265 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2B	NM_032559.5 link	c.769C>T	p.Arg257Cys	missense_variant	Exon 1 of 1	ENST00000268919.6	NP_115948.4	Q8N4N8A0A140VKG5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2B	ENST00000268919.6 link	c.769C>T	p.Arg257Cys	missense_variant	Exon 1 of 1	6	NM_032559.5	ENSP00000268919.4		Q8N4N8
ENSG00000285939	ENST00000650577.1 link	n.659+16030G>A		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

265

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0170

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00188

AC:

473

AN:

251464

Hom.:

AF XY:

0.00186

AC XY:

253

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.000925

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0158

Gnomad SAS exome

AF:

0.00235

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.000849

AC:

1241

AN:

1461892

Hom.:

Cov.:

AF XY:

0.000931

AC XY:

677

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00421

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0131

Gnomad4 SAS exome

AF:

0.00261

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00174

AC:

265

AN:

152332

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0168

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000902

Hom.:

Bravo

AF:

0.00192

ESP6500AA

AF:

0.00272

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00195

AC:

237

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Benign

0.38

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.011

MetaSVM

Uncertain

-0.19

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.9

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.87

MPC

0.59

ClinPred

0.057

GERP RS

5.5

Varity_R

0.44

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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