5-62347989-G-A

Position:

• chr5-62347989-G-A

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.160-59G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 1,550,174 control chromosomes in the GnomAD database, including 147,794 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19079 hom., cov: 32)
  • Exomes 𝑓: 0.42 (128715 hom.)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.484

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=-0.87).
• BP6: Variant 5-62347989-G-A is Benign according to our data. Variant chr5-62347989-G-A is described in ClinVar as [Benign]. Clinvar id is 682855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.160-59G>A		intron_variant		ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.160-59G>A		intron_variant			NP_004511.2
KIF2A	NM_001243953.2	c.160-59G>A		intron_variant			NP_001230882.1
KIF2A	NM_001243952.2	c.79-59G>A		intron_variant			NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8	c.160-59G>A		intron_variant		1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.64+41453G>A		intron_variant		3		ENSP00000502199.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74106 AN: 151840 Hom.: 19039 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.444

GnomAD4 exome AF: 0.424 AC: 593244 AN: 1398216 Hom.: 128715 AF XY: 0.421 AC XY: 292351 AN XY: 693682

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.460

Gnomad4 ASJ exome AF: 0.475

Gnomad4 EAS exome AF: 0.620

Gnomad4 SAS exome AF: 0.347

Gnomad4 FIN exome AF: 0.445

Gnomad4 NFE exome AF: 0.412

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.488 AC: 74198 AN: 151958 Hom.: 19079 Cov.: 32 AF XY: 0.488 AC XY: 36220 AN XY: 74270

Gnomad4 AFR AF: 0.642

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.624

Gnomad4 SAS AF: 0.353

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.410

Gnomad4 OTH AF: 0.442

Alfa AF: 0.449 Hom.: 1996

Bravo AF: 0.500

Asia WGS AF: 0.506 AC: 1762 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	-0.87
CADD	Benign	0.72
DANN	Benign	0.46

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: rs3776615; hg19: chr5-61643816; COSMIC: COSV66944898;