rs186886643

Variant names:

• chr17-53823535-C-A
• rs186886643
• NM_032559.5:c.502C>A

Your query was ambiguous. Multiple possible variants found:

• chr17-53823535-C-A
• chr17-53823535-C-G
• chr17-53823535-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032559.5(KIF2B):​c.502C>A​(p.Gln168Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,613,836 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q168L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00040 (0 hom.)
• Consequence: KIF2B NM_032559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355
• Publications: 3 publications found

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]

ENSG00000285939 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.029271811).
• BS2: High AC in GnomAd4 at 30 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.502C>A	p.Gln168Lys	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.502C>A	p.Gln168Lys	missense	Exon 1 of 1	ENSP00000268919.4	Q8N4N8
	ENSG00000285939	ENST00000650577.1		n.659+16297G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000197 AC: 30 AN: 152218 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

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: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000188 AC: 47 AN: 249994 AF XY: 0.000214

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000188

Gnomad NFE exome AF: 0.000372

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000402 AC: 588 AN: 1461500 Hom.: 0 Cov.: 74 AF XY: 0.000382 AC XY: 278 AN XY: 727060

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.000189 AC: 10 AN: 53028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000498 AC: 554 AN: 1112010

Other (OTH) AF: 0.000315 AC: 19 AN: 60396

GnomAD4 genome AF: 0.000197 AC: 30 AN: 152336 Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8 AN XY: 74482

African (AFR) AF: 0.0000721 AC: 3 AN: 41584

American (AMR) AF: 0.00 AC: 0 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000213 Hom.: 0

Bravo AF: 0.000144

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.000198 AC: 24

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.7
DANN	Benign	0.53
DEOGEN2	Benign	0.0084	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.35
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.083
Sift	Benign	0.65	T
Sift4G	Benign	0.93	T
Polyphen		0.027	B
Vest4		0.15
MVP		0.75
MPC		0.13
ClinPred		0.019	T
GERP RS		-0.35
Varity_R		0.12
gMVP		0.46
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs186886643; hg19: chr17-51900896;