5-62306223-C-G

Variant names:

• chr5-62306223-C-G
• rs141968809
• NM_001098511.3:c.-250C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001098511.3(KIF2A):​c.-250C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000325 in 307,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.298
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

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.-250C>G		5_prime_UTR	Exon 1 of 21	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.-250C>G		5_prime_UTR	Exon 1 of 20	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.-250C>G		5_prime_UTR	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.-250C>G		5_prime_UTR	Exon 1 of 21	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.-250C>G		5_prime_UTR	Exon 1 of 20	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000514082.6	TSL:1	c.-250C>G		5_prime_UTR	Exon 1 of 14	ENSP00000423542.2	D6R9M0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000325 AC: 1 AN: 307872 Hom.: 0 Cov.: 0 AF XY: 0.00000617 AC XY: 1 AN XY: 161996

African (AFR) AF: 0.00 AC: 0 AN: 6370

American (AMR) AF: 0.00 AC: 0 AN: 6848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9524

East Asian (EAS) AF: 0.00 AC: 0 AN: 20746

South Asian (SAS) AF: 0.00 AC: 0 AN: 26156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1464

European-Non Finnish (NFE) AF: 0.00000519 AC: 1 AN: 192580

Other (OTH) AF: 0.00 AC: 0 AN: 18728

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	15
DANN	Benign	0.73
PhyloP100		0.30
PromoterAI		0.092	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs141968809; hg19: chr5-61602050;