rs152189

Positions:

• chr5-62384621-T-C
• chr5-62384621-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098511.3(KIF2A):​c.2150-863T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,128 control chromosomes in the GnomAD database, including 4,697 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 0.25 (4697 hom., cov: 32)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

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]

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.2150-863T>C		intron_variant		ENST00000407818.8
KIF2A	NM_001243952.2	c.1955-863T>C		intron_variant
KIF2A	NM_001243953.2	c.1979-863T>C		intron_variant
KIF2A	NM_004520.5	c.2036-863T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.2150-863T>C		intron_variant		1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37455 AN: 152010 Hom.: 4697 Cov.: 32

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.246 AC: 37472 AN: 152128 Hom.: 4697 Cov.: 32 AF XY: 0.245 AC XY: 18258 AN XY: 74378

Gnomad4 AFR AF: 0.263

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.218

Alfa AF: 0.241 Hom.: 749

Bravo AF: 0.247

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.54
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs152189; hg19: chr5-61680448;