chr5-62306499-C-A

Variant names:

• chr5-62306499-C-A
• rs1745280504
• NM_001098511.3:c.27C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001098511.3(KIF2A):​c.27C>A​(p.Ile9Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000574 in 1,392,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. I9I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: KIF2A NM_001098511.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B: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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 5-62306499-C-A is Benign according to our data. Variant chr5-62306499-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1559088.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.862 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.27C>A	p.Ile9Ile	synonymous	Exon 1 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.27C>A	p.Ile9Ile	synonymous	Exon 1 of 20	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.27C>A	p.Ile9Ile	synonymous	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.27C>A	p.Ile9Ile	synonymous	Exon 1 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.27C>A	p.Ile9Ile	synonymous	Exon 1 of 20	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000514082.6	TSL:1	c.27C>A	p.Ile9Ile	synonymous	Exon 1 of 14	ENSP00000423542.2	D6R9M0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000574 AC: 8 AN: 1392874 Hom.: 0 Cov.: 32 AF XY: 0.0000102 AC XY: 7 AN XY: 686944

African (AFR) AF: 0.00 AC: 0 AN: 30720

American (AMR) AF: 0.00 AC: 0 AN: 35278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24944

East Asian (EAS) AF: 0.00 AC: 0 AN: 35272

South Asian (SAS) AF: 0.0000382 AC: 3 AN: 78448

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5674

European-Non Finnish (NFE) AF: 0.00000465 AC: 5 AN: 1076216

Other (OTH) AF: 0.00 AC: 0 AN: 57702

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000624 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.93
PhyloP100		0.86
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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;