5-62306499-C-G

Variant names:

• chr5-62306499-C-G
• rs1745280504
• ENST00000381103.7:c.-258C>G

Variant summary

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

The NM_001243952.2(KIF2A):​c.-258C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KIF2A NM_001243952.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.862
• Publications: 0 publications found

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]

KIF2A Gene-Disease associations (from GenCC):

• complex cortical dysplasia with other brain malformations 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ENSG00000288643 (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_001243952.2. 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
	KIF2A	NM_001098511.3	MANE Select	c.27C>G	p.Ile9Met	missense	Exon 1 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_001243952.2		c.-258C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	NP_001230881.2	O00139-1
	KIF2A	NM_004520.5		c.27C>G	p.Ile9Met	missense	Exon 1 of 20	NP_004511.2	O00139-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	ENST00000381103.7	TSL:1	c.-258C>G		5_prime_UTR_premature_start_codon_gain	Exon 1 of 21	ENSP00000370493.3	O00139-1
	KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.27C>G	p.Ile9Met	missense	Exon 1 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.27C>G	p.Ile9Met	missense	Exon 1 of 20	ENSP00000385622.3	O00139-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.086	D
BayesDel_noAF	Benign	-0.11
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.064	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.11	N
LIST_S2	Uncertain	0.90	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.86
PrimateAI	Pathogenic	0.92	D
PROVEAN	Benign	-0.99	N
REVEL	Uncertain	0.31
Sift	Benign	0.068	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.41
MutPred		0.53		Loss of methylation at K8 (P = 0.0222)
MVP		0.82
MPC		1.9
ClinPred		0.87	D
GERP RS		2.3
PromoterAI		-0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.59
Mutation Taster		=76/24	polymorphism

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: rs1745280504; hg19: chr5-61602326;