5-62347834-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098511.3(KIF2A):c.160-214G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 151,922 control chromosomes in the GnomAD database, including 771 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.090 (771 hom., cov: 31)
• Consequence: KIF2A NM_001098511.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441

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]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 5-62347834-G-A is Benign according to our data. Variant chr5-62347834-G-A is described in ClinVar as [Benign]. Clinvar id is 672374.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.160-214G>A		intron_variant		ENST00000407818.8
KIF2A	NM_001243952.2	c.79-214G>A		intron_variant
KIF2A	NM_001243953.2	c.160-214G>A		intron_variant
KIF2A	NM_004520.5	c.160-214G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.160-214G>A		intron_variant		1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.0898 AC: 13629 AN: 151804 Hom.: 769 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00440

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0542

Gnomad EAS AF: 0.0355

Gnomad SAS AF: 0.132

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0653

Gnomad OTH AF: 0.0849

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0897 AC: 13635 AN: 151922 Hom.: 771 Cov.: 31 AF XY: 0.0884 AC XY: 6566 AN XY: 74250

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0737

Gnomad4 ASJ AF: 0.0542

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.132

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.0653

Gnomad4 OTH AF: 0.0836

Alfa AF: 0.0758 Hom.: 67

Bravo AF: 0.0941

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	-0.95
Cadd	Benign	2.4
Dann	Benign	0.67

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: rs3776613; hg19: chr5-61643661;