5-62377843-A-G

Variant names:

• chr5-62377843-A-G
• rs464058
• NM_001098511.3:c.2013+81A>G

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.2013+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 775,798 control chromosomes in the GnomAD database, including 24,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (4884 hom., cov: 33)
  • Exomes 𝑓: 0.25 (20005 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0120
• Publications: 4 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=-0.85).
• BP6: Variant 5-62377843-A-G is Benign according to our data. Variant chr5-62377843-A-G is described in ClinVar as Benign. ClinVar VariationId is 682886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	NM_001098511.3	MANE Select	c.2013+81A>G		intron	N/A	NP_001091981.1
	KIF2A	NM_004520.5		c.1899+81A>G		intron	N/A	NP_004511.2
	KIF2A	NM_001243953.2		c.1842+81A>G		intron	N/A	NP_001230882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.2013+81A>G		intron	N/A	ENSP00000385000.3
	KIF2A	ENST00000401507.7	TSL:1	c.1899+81A>G		intron	N/A	ENSP00000385622.3
	KIF2A	ENST00000381103.7	TSL:1	c.1818+81A>G		intron	N/A	ENSP00000370493.3

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38122 AN: 152038 Hom.: 4884 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.222

GnomAD4 exome AF: 0.249 AC: 155587 AN: 623642 Hom.: 20005 AF XY: 0.249 AC XY: 80709 AN XY: 324594

African (AFR) AF: 0.264 AC: 4088 AN: 15480

American (AMR) AF: 0.198 AC: 4150 AN: 20950

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 4640 AN: 16388

East Asian (EAS) AF: 0.280 AC: 8595 AN: 30740

South Asian (SAS) AF: 0.191 AC: 8257 AN: 43144

European-Finnish (FIN) AF: 0.258 AC: 11485 AN: 44476

Middle Eastern (MID) AF: 0.278 AC: 944 AN: 3396

European-Non Finnish (NFE) AF: 0.253 AC: 105885 AN: 418002

Other (OTH) AF: 0.243 AC: 7543 AN: 31066

GnomAD4 genome AF: 0.251 AC: 38139 AN: 152156 Hom.: 4884 Cov.: 33 AF XY: 0.250 AC XY: 18630 AN XY: 74394

African (AFR) AF: 0.265 AC: 10987 AN: 41518

American (AMR) AF: 0.204 AC: 3122 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3468

East Asian (EAS) AF: 0.231 AC: 1198 AN: 5190

South Asian (SAS) AF: 0.183 AC: 883 AN: 4820

European-Finnish (FIN) AF: 0.249 AC: 2626 AN: 10562

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17390 AN: 67984

Other (OTH) AF: 0.221 AC: 467 AN: 2110

Alfa AF: 0.252 Hom.: 788

Bravo AF: 0.250

Asia WGS AF: 0.198 AC: 691 AN: 3478

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.75
DANN	Benign	0.62
PhyloP100		0.012
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: rs464058; hg19: chr5-61673670;