NM_001098511.3:c.2150-1699C>T

Variant names:

• chr5-62383785-C-T
• rs153867
• NM_001098511.3:c.2150-1699C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001098511.3(KIF2A):​c.2150-1699C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0301 in 152,206 control chromosomes in the GnomAD database, including 100 homozygotes. 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: 𝑓 0.030 (100 hom., cov: 32)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 6 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]

ENSG00000288643 (HGNC:):

DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0301 (4587/152206) while in subpopulation NFE AF = 0.0458 (3114/68000). AF 95% confidence interval is 0.0445. There are 100 homozygotes in GnomAd4. There are 2206 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 4587 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.2150-1699C>T		intron	N/A	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.2036-1699C>T		intron	N/A	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.1979-1699C>T		intron	N/A	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.2150-1699C>T		intron	N/A	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.2036-1699C>T		intron	N/A	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000381103.7	TSL:1	c.1955-1699C>T		intron	N/A	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes AF: 0.0302 AC: 4588 AN: 152088 Hom.: 100 Cov.: 32

Gnomad AFR AF: 0.00874

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.0164

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0205

Gnomad FIN AF: 0.0492

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0458

Gnomad OTH AF: 0.0211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0301 AC: 4587 AN: 152206 Hom.: 100 Cov.: 32 AF XY: 0.0296 AC XY: 2206 AN XY: 74414

African (AFR) AF: 0.00871 AC: 362 AN: 41544

American (AMR) AF: 0.0164 AC: 251 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4824

European-Finnish (FIN) AF: 0.0492 AC: 521 AN: 10580

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0458 AC: 3114 AN: 68000

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.0389 Hom.: 208

Bravo AF: 0.0271

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.42
PhyloP100		-0.32
Mutation Taster		=100/0	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: rs153867; hg19: chr5-61679612;