5-62306491-G-A

Position:

• chr5-62306491-G-A

Variant summary

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

The NM_001098511.3(KIF2A):​c.19G>A​(p.Gly7Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000144 in 1,393,330 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIF2A NM_001098511.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.48

Genes affected

KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288643 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.19G>A	p.Gly7Ser	missense_variant	1/21	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.19G>A	p.Gly7Ser	missense_variant	1/20		NP_004511.2
KIF2A	NM_001243953.2	c.19G>A	p.Gly7Ser	missense_variant	1/20		NP_001230882.1
KIF2A	NM_001243952.2	c.-266G>A		5_prime_UTR_variant	1/21		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.19G>A	p.Gly7Ser	missense_variant	1/21	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.19G>A		non_coding_transcript_exon_variant	1/6	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000144 AC: 2 AN: 1393330 Hom.: 0 Cov.: 32 AF XY: 0.00000146 AC XY: 1 AN XY: 687178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000186

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 29, 2023

This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 7 of the KIF2A protein (p.Gly7Ser). This variant has not been reported in the literature in individuals affected with KIF2A-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.87
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T;T;.
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.47	T;T;T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L;.;L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N;N;N
REVEL	Benign	0.27
Sift	Benign	0.081	T;D;D
Sift4G	Benign	0.26	T;T;T
Polyphen		1.0	D;.;D
Vest4		0.45
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);
MVP		0.92
MPC		1.9
ClinPred		0.97	D
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.59

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: rs552269440; hg19: chr5-61602318;