chr5-62377843-A-G

Position:

• chr5-62377843-A-G

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.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

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=-0.85).
• BP6: Variant 5-62377843-A-G is Benign according to our data. Variant chr5-62377843-A-G is described in ClinVar as [Benign]. Clinvar id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.2013+81A>G		intron_variant		ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.1899+81A>G		intron_variant			NP_004511.2
KIF2A	NM_001243953.2	c.1842+81A>G		intron_variant			NP_001230882.1
KIF2A	NM_001243952.2	c.1818+81A>G		intron_variant			NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.2013+81A>G		intron_variant		1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+71307A>G		intron_variant		3		ENSP00000502199.1

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

Gnomad4 AFR exome AF: 0.264

Gnomad4 AMR exome AF: 0.198

Gnomad4 ASJ exome AF: 0.283

Gnomad4 EAS exome AF: 0.280

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.258

Gnomad4 NFE exome AF: 0.253

Gnomad4 OTH exome AF: 0.243

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

Gnomad4 AFR AF: 0.265

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.231

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.221

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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	-0.85
CADD	Benign	0.75
DANN	Benign	0.62

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: rs464058; hg19: chr5-61673670;