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

Variant summary

Our verdict is Benign. The variant received -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

Publications

7 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 789094.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 265 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032559.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2B	NM_032559.5	MANE Select	c.769C>T	p.Arg257Cys	missense	Exon 1 of 1	NP_115948.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2B	ENST00000268919.6	TSL:6 MANE Select	c.769C>T	p.Arg257Cys	missense	Exon 1 of 1	ENSP00000268919.4	Q8N4N8
	ENSG00000285939	ENST00000650577.1		n.659+16030G>A		intron	N/A

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

GnomAD2 exomes

AF:

0.00188

AC:

473

AN:

251464

AF XY:

0.00186

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 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

African (AFR)

AF:

0.00421

AC:

141

AN:

33480

American (AMR)

AF:

0.000939

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0131

AC:

520

AN:

39700

South Asian (SAS)

AF:

0.00261

AC:

225

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000140

AC:

156

AN:

1112012

Other (OTH)

AF:

0.00242

AC:

146

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

182

272

363

454

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00174

AC:

265

AN:

152332

Hom.:

Cov.:

AF XY:

0.00180

AC XY:

134

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00322

AC:

134

AN:

41574

American (AMR)

AF:

0.000719

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0168

AC:

AN:

5178

South Asian (SAS)

AF:

0.00290

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68032

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00105

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

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

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

PhyloP100

-0.099

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

Mutation Taster

=78/22

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over