rs153867

chr5-62383785-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.9).
• 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 male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 4588 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.2150-1699C>T		intron_variant		ENST00000407818.8
KIF2A	NM_001243952.2	c.1955-1699C>T		intron_variant
KIF2A	NM_001243953.2	c.1979-1699C>T		intron_variant
KIF2A	NM_004520.5	c.2036-1699C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.2150-1699C>T		intron_variant		1	NM_001098511.3	A1

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

Gnomad4 AFR AF: 0.00871

Gnomad4 AMR AF: 0.0164

Gnomad4 ASJ AF: 0.0423

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0203

Gnomad4 FIN AF: 0.0492

Gnomad4 NFE AF: 0.0458

Gnomad4 OTH AF: 0.0208

Alfa AF: 0.0411 Hom.: 157

Bravo AF: 0.0271

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	2.2
Dann	Benign	0.42

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: rs153867; hg19: chr5-61679612;