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. Variant got -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

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

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.559-143G>A		intron_variant	Intron 6 of 20	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.559-143G>A		intron_variant	Intron 6 of 19		NP_004511.2
KIF2A	NM_001243953.2	c.502-143G>A		intron_variant	Intron 6 of 19		NP_001230882.1
KIF2A	NM_001243952.2	c.478-143G>A		intron_variant	Intron 7 of 20		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.559-143G>A		intron_variant	Intron 6 of 20	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+48480G>A		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

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

Gnomad4 AFR exome AF: 0.615

Gnomad4 AMR exome AF: 0.438

Gnomad4 ASJ exome AF: 0.471

Gnomad4 EAS exome AF: 0.617

Gnomad4 SAS exome AF: 0.337

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.402

Gnomad4 OTH exome AF: 0.442

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

Gnomad4 AFR AF: 0.617

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.441

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.435

Alfa AF: 0.423 Hom.: 14346

Bravo AF: 0.492

Asia WGS AF: 0.503 AC: 1750 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.27
DANN	Benign	0.51

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: rs2289883; hg19: chr5-61650843;