17-53823361-C-G

Variant names:

• chr17-53823361-C-G
• rs771284173
• NM_032559.5:c.328C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_032559.5(KIF2B):​c.328C>G​(p.Arg110Gly) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF2B NM_032559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.04

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.051291376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2B	NM_032559.5	c.328C>G	p.Arg110Gly	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.328C>G	p.Arg110Gly	missense_variant	Exon 1 of 1	6	NM_032559.5	ENSP00000268919.4
ENSG00000285939	ENST00000650577.1	n.659+16471G>C		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 17, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.328C>G (p.R110G) alteration is located in exon 1 (coding exon 1) of the KIF2B gene. This alteration results from a C to G substitution at nucleotide position 328, causing the arginine (R) at amino acid position 110 to be replaced by a glycine (G). 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	0.079
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	2.5
DANN	Benign	0.50
DEOGEN2	Benign	0.0080	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.051	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.13
Sift	Benign	0.048	D
Sift4G	Benign	0.15	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.30		Loss of MoRF binding (P = 0.0191);
MVP		0.34
MPC		0.13
ClinPred		0.10	T
GERP RS		-9.2
Varity_R		0.084
gMVP		0.21

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

Other links and lift over

dbSNP: rs771284173; hg19: chr17-51900722;