5-62348083-C-A

Position:

chr5-62348083-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001098511.3(KIF2A):c.195C>A(p.Asp65Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,613,756 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 9 hom. )

Consequence

KIF2A
NM_001098511.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.83

Variant links:

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]

KIF2A links:

ENSG00000288643 (HGNC:):

ENSG00000288643 links:

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]

DIMT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007913381).

BP6

Variant 5-62348083-C-A is Benign according to our data. Variant chr5-62348083-C-A is described in ClinVar as [Benign]. Clinvar id is 382901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00627 (955/152276) while in subpopulation AFR AF= 0.0221 (918/41548). AF 95% confidence interval is 0.0209. There are 8 homozygotes in gnomad4. There are 464 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 955 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3 linkuse as main transcript	c.195C>A	p.Asp65Glu	missense_variant	3/21	ENST00000407818.8	NP_001091981.1	O00139-4
KIF2A	NM_004520.5 linkuse as main transcript	c.195C>A	p.Asp65Glu	missense_variant	3/20		NP_004511.2	O00139-3
KIF2A	NM_001243953.2 linkuse as main transcript	c.195C>A	p.Asp65Glu	missense_variant	3/20		NP_001230882.1	A0A6Q8PFA6B0AZS5
KIF2A	NM_001243952.2 linkuse as main transcript	c.114C>A	p.Asp38Glu	missense_variant	4/21		NP_001230881.2	O00139-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8 linkuse as main transcript	c.195C>A	p.Asp65Glu	missense_variant	3/21	1	NM_001098511.3	ENSP00000385000.3		O00139-4
ENSG00000288643	ENST00000509663.2 linkuse as main transcript	n.64+41547C>A		intron_variant		3		ENSP00000502199.1		A0A6Q8PGD0

Frequencies

GnomAD3 genomes

AF:

0.00627

AC:

954

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0221

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00158

AC:

397

AN:

251154

Hom.:

AF XY:

0.00119

AC XY:

161

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.0226

Gnomad AMR exome

AF:

0.000752

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000629

AC:

919

AN:

1461480

Hom.:

Cov.:

AF XY:

0.000552

AC XY:

401

AN XY:

727036

show subpopulations

Gnomad4 AFR exome

AF:

0.0238

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00118

GnomAD4 genome

AF:

0.00627

AC:

955

AN:

152276

Hom.:

Cov.:

AF XY:

0.00623

AC XY:

464

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00124

Hom.:

Bravo

AF:

0.00703

ESP6500AA

AF:

0.0207

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00194

AC:

235

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 24, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 02, 2016

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. -

KIF2A-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 31, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

T;.;T;.;.;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.038

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

D;D;T;D;D;T

MetaRNN

Benign

0.0079

T;T;T;T;T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.73

N;.;.;N;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-1.6

N;N;N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.81

T;T;T;T;D;T

Sift4G

Benign

0.66

T;T;T;T;D;T

Polyphen

0.44

B;.;.;B;.;.

Vest4

0.57

MutPred

0.12

Gain of phosphorylation at S61 (P = 0.191);.;Gain of phosphorylation at S61 (P = 0.191);Gain of phosphorylation at S61 (P = 0.191);.;.;

MVP

0.47

MPC

1.4

ClinPred

0.019

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.15

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over