chr17-53823548-C-T

Variant names:

• chr17-53823548-C-T
• NM_032559.5:c.515C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032559.5(KIF2B):​c.515C>T​(p.Ala172Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF2B NM_032559.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19144163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2B	NM_032559.5	c.515C>T	p.Ala172Val	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.515C>T	p.Ala172Val	missense_variant	Exon 1 of 1	6	NM_032559.5	ENSP00000268919.4
ENSG00000285939	ENST00000650577.1	n.659+16284G>A		intron_variant	Intron 4 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 74

GnomAD4 genome Cov.: 33

EpiCase AF: 0.000109

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.515C>T (p.A172V) 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 515, causing the alanine (A) at amino acid position 172 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	0.10
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.061
Eigen_PC	Benign	-0.047
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.12
Sift	Benign	0.20	T
Sift4G	Benign	0.21	T
Polyphen		0.75	P
Vest4		0.30
MutPred		0.28		Loss of helix (P = 0.1299);
MVP		0.78
MPC		0.28
ClinPred		0.62	D
GERP RS		4.5
Varity_R		0.057
gMVP		0.35

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-51900909;