17-53823659-C-A

Variant names:

• chr17-53823659-C-A
• rs1275391820
• NM_032559.5:c.626C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032559.5(KIF2B):​c.626C>A​(p.Pro209Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. P209L) 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: -1.62
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05805126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2B	NM_032559.5	c.626C>A	p.Pro209Gln	missense_variant	Exon 1 of 1	ENST00000268919.6	NP_115948.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2B	ENST00000268919.6	c.626C>A	p.Pro209Gln	missense_variant	Exon 1 of 1	6	NM_032559.5	ENSP00000268919.4
ENSG00000285939	ENST00000650577.1	n.659+16173G>T		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.10
DANN	Benign	0.75
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		-1.6
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.0010
Sift	Benign	0.037	D
Sift4G	Uncertain	0.027	D
Polyphen		0.050	B
Vest4		0.14
MutPred		0.27		Loss of catalytic residue at P208 (P = 0.0225);
MVP		0.21
MPC		0.091
ClinPred		0.086	T
GERP RS		-4.7
Varity_R		0.026
gMVP		0.26

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: rs1275391820; hg19: chr17-51901020; COSMIC: COSV107281278;