5-62306223-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001098511.3(KIF2A):​c.-250C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 459,908 control chromosomes in the GnomAD database, including 1,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.061 (436 hom., cov: 33)
  • Exomes 𝑓: 0.072 (982 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-62306223-C-T is Benign according to our data. Variant chr5-62306223-C-T is described in ClinVar as Benign. ClinVar VariationId is 1222402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

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

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9240 AN: 152086 Hom.: 436 Cov.: 33

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0718 AC: 22102 AN: 307714 Hom.: 982 Cov.: 0 AF XY: 0.0706 AC XY: 11440 AN XY: 161926

African (AFR) AF: 0.0163 AC: 104 AN: 6366

American (AMR) AF: 0.0661 AC: 452 AN: 6842

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 1335 AN: 9518

East Asian (EAS) AF: 0.0000482 AC: 1 AN: 20746

South Asian (SAS) AF: 0.0356 AC: 931 AN: 26148

European-Finnish (FIN) AF: 0.0552 AC: 1404 AN: 25442

Middle Eastern (MID) AF: 0.125 AC: 183 AN: 1462

European-Non Finnish (NFE) AF: 0.0843 AC: 16220 AN: 192470

Other (OTH) AF: 0.0786 AC: 1472 AN: 18720

GnomAD4 genome AF: 0.0607 AC: 9241 AN: 152194 Hom.: 436 Cov.: 33 AF XY: 0.0591 AC XY: 4396 AN XY: 74400

African (AFR) AF: 0.0140 AC: 584 AN: 41568

American (AMR) AF: 0.0718 AC: 1097 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 519 AN: 3472

East Asian (EAS) AF: 0.000582 AC: 3 AN: 5152

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4830

European-Finnish (FIN) AF: 0.0617 AC: 654 AN: 10600

Middle Eastern (MID) AF: 0.127 AC: 37 AN: 292

European-Non Finnish (NFE) AF: 0.0854 AC: 5804 AN: 67970

Other (OTH) AF: 0.0710 AC: 150 AN: 2112

Alfa AF: 0.0276 Hom.: 16

Bravo AF: 0.0607

Asia WGS AF: 0.0190 AC: 64 AN: 3456

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.80
PhyloP100		0.30
PromoterAI		-0.11	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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;