rs2289883

Variant names:

• chr5-62355016-G-A
• rs2289883
• NM_001098511.3:c.559-143G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-62355016-G-A
• chr5-62355016-G-C

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.559-143G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 512,836 control chromosomes in the GnomAD database, including 52,864 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18422 hom., cov: 32)
  • Exomes 𝑓: 0.43 (34442 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.71
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-62355016-G-A is Benign according to our data. Variant chr5-62355016-G-A is described in ClinVar as Benign. ClinVar VariationId is 682867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 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.559-143G>A		intron	N/A	NP_001091981.1	O00139-4
	KIF2A	NM_004520.5		c.559-143G>A		intron	N/A	NP_004511.2	O00139-3
	KIF2A	NM_001243953.2		c.502-143G>A		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.559-143G>A		intron	N/A	ENSP00000385000.3	O00139-4
	KIF2A	ENST00000401507.7	TSL:1	c.559-143G>A		intron	N/A	ENSP00000385622.3	O00139-3
	KIF2A	ENST00000381103.7	TSL:1	c.478-143G>A		intron	N/A	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes AF: 0.481 AC: 73057 AN: 151862 Hom.: 18386 Cov.: 32

Gnomad AFR AF: 0.617

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.437

GnomAD4 exome AF: 0.428 AC: 154491 AN: 360856 Hom.: 34442 AF XY: 0.423 AC XY: 80318 AN XY: 189790

African (AFR) AF: 0.615 AC: 5410 AN: 8800

American (AMR) AF: 0.438 AC: 5060 AN: 11552

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 5309 AN: 11266

East Asian (EAS) AF: 0.617 AC: 15846 AN: 25672

South Asian (SAS) AF: 0.337 AC: 8109 AN: 24098

European-Finnish (FIN) AF: 0.443 AC: 16730 AN: 37806

Middle Eastern (MID) AF: 0.408 AC: 676 AN: 1656

European-Non Finnish (NFE) AF: 0.402 AC: 88001 AN: 218850

Other (OTH) AF: 0.442 AC: 9350 AN: 21156

GnomAD4 genome AF: 0.481 AC: 73147 AN: 151980 Hom.: 18422 Cov.: 32 AF XY: 0.481 AC XY: 35744 AN XY: 74284

African (AFR) AF: 0.617 AC: 25594 AN: 41458

American (AMR) AF: 0.452 AC: 6894 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1699 AN: 3472

East Asian (EAS) AF: 0.626 AC: 3240 AN: 5178

South Asian (SAS) AF: 0.353 AC: 1701 AN: 4824

European-Finnish (FIN) AF: 0.441 AC: 4656 AN: 10550

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27834 AN: 67928

Other (OTH) AF: 0.435 AC: 917 AN: 2106

Alfa AF: 0.426 Hom.: 17498

Bravo AF: 0.492

Asia WGS AF: 0.503 AC: 1750 AN: 3474

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	-0.92
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		-1.7
Mutation Taster		=100/0	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: rs2289883; hg19: chr5-61650843;