17-53823290-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032559.5(KIF2B):​c.257C>T​(p.Ala86Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

KIF2B
NM_032559.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.215
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.069973886).
BS2
High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIF2BNM_032559.5 linkc.257C>T p.Ala86Val 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
KIF2BENST00000268919.6 linkc.257C>T p.Ala86Val missense_variant Exon 1 of 1 6 NM_032559.5 ENSP00000268919.4 Q8N4N8
ENSG00000285939ENST00000650577.1 linkn.659+16542G>A intron_variant Intron 4 of 6

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251360
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000352
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461888
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000989
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000416
ExAC
AF:
0.0000330
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 29, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.257C>T (p.A86V) alteration is located in exon 1 (coding exon 1) of the KIF2B gene. This alteration results from a C to T substitution at nucleotide position 257, causing the alanine (A) at amino acid position 86 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
3.6
DANN
Benign
0.94
DEOGEN2
Benign
0.0059
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.85
FATHMM_MKL
Benign
0.16
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.070
T
MetaSVM
Benign
-0.92
T
MutationAssessor
Benign
1.4
L
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.46
N
REVEL
Benign
0.053
Sift
Benign
0.29
T
Sift4G
Benign
0.29
T
Polyphen
0.0040
B
Vest4
0.13
MVP
0.73
MPC
0.10
ClinPred
0.025
T
GERP RS
2.9
Varity_R
0.027
gMVP
0.23

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: rs750373414; hg19: chr17-51900651; API