17-53823556-G-C

Variant names:

• chr17-53823556-G-C
• rs149901637
• NM_032559.5:c.523G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_032559.5(KIF2B):​c.523G>C​(p.Ala175Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A175S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF2B NM_032559.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.58
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.523G>C	p.Ala175Pro	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.523G>C	p.Ala175Pro	missense	Exon 1 of 1	ENSP00000268919.4	Q8N4N8
	ENSG00000285939	ENST00000650577.1		n.659+16276C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.053	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.020	T
MetaRNN	Uncertain	0.48	T
MetaSVM	Uncertain	0.12	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		2.6
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.29
Sift	Uncertain	0.012	D
Sift4G	Benign	0.12	T
Polyphen		1.0	D
Vest4		0.37
MutPred		0.40		Loss of helix (P = 0.0068)
MVP		0.67
MPC		0.56
ClinPred		0.98	D
GERP RS		5.5
Varity_R		0.61
gMVP		0.62

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: rs149901637; hg19: chr17-51900917;