rs552269440

Variant names:

• chr5-62306491-G-A
• rs552269440
• NM_001098511.3:c.19G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-62306491-G-A
• chr5-62306491-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G7R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: KIF2A NM_001098511.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 5.48
• Publications: 1 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_001098511.3. 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.19G>A	p.Gly7Ser	missense	Exon 1 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.19G>A	p.Gly7Ser	missense	Exon 1 of 20	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.19G>A	p.Gly7Ser	missense	Exon 1 of 20	NP_001230882.1	A0A6Q8PFA6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.19G>A	p.Gly7Ser	missense	Exon 1 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.19G>A	p.Gly7Ser	missense	Exon 1 of 20	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000514082.6	TSL:1	c.19G>A	p.Gly7Ser	missense	Exon 1 of 14	ENSP00000423542.2	D6R9M0

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

African (AFR) AF: 0.00 AC: 0 AN: 30626

American (AMR) AF: 0.00 AC: 0 AN: 35242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24980

East Asian (EAS) AF: 0.00 AC: 0 AN: 35214

South Asian (SAS) AF: 0.00 AC: 0 AN: 78310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48726

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 0.00000186 AC: 2 AN: 1076786

Other (OTH) AF: 0.00 AC: 0 AN: 57766

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.58	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.99	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Benign	-0.44	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.27
Sift	Benign	0.081	T
Sift4G	Benign	0.26	T
Polyphen		1.0	D
Vest4		0.45
MutPred		0.48		Gain of relative solvent accessibility (P = 0.0479)
MVP		0.92
MPC		1.9
ClinPred		0.97	D
GERP RS		3.4
PromoterAI		-0.085	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.59
Mutation Taster		=68/32	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: rs552269440; hg19: chr5-61602318;