chr5-62348114-C-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001098511.3(KIF2A):c.226C>A(p.Pro76Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,613,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

KIF2A
NM_001098511.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.63

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018188715).

BP6

Variant 5-62348114-C-A is Benign according to our data. Variant chr5-62348114-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 384104.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 6 AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF2A	NM_001098511.3	MANE Select	c.226C>A	p.Pro76Thr	missense	Exon 3 of 21	NP_001091981.1	O00139-4
KIF2A	NM_004520.5		c.226C>A	p.Pro76Thr	missense	Exon 3 of 20	NP_004511.2	O00139-3
KIF2A	NM_001243953.2		c.226C>A	p.Pro76Thr	missense	Exon 3 of 20	NP_001230882.1	A0A6Q8PFA6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIF2A	ENST00000407818.8	TSL:1 MANE Select	c.226C>A	p.Pro76Thr	missense	Exon 3 of 21	ENSP00000385000.3	O00139-4
KIF2A	ENST00000401507.7	TSL:1	c.226C>A	p.Pro76Thr	missense	Exon 3 of 20	ENSP00000385622.3	O00139-3
KIF2A	ENST00000381103.7	TSL:1	c.145C>A	p.Pro49Thr	missense	Exon 4 of 21	ENSP00000370493.3	O00139-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000315

AC:

AN:

251128

AF XY:

0.000258

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00225

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1461550

Hom.:

Cov.:

AF XY:

0.0000550

AC XY:

AN XY:

727060

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00190

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.00

AC:

AN:

86242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111782

Other (OTH)

AF:

0.00

AC:

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.420

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152108

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41400

American (AMR)

AF:

0.000393

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.433

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.000321

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

KIF2A-related disorder (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

Eigen

Benign

0.076

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.051

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.50

MutationAssessor

Benign

1.9

PhyloP100

4.6

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.18

Sift

Benign

0.073

Sift4G

Benign

0.061

Polyphen

0.0030

Vest4

0.39

MutPred

0.18

Gain of phosphorylation at P76 (P = 0.0123)

MVP

0.64

MPC

1.1

ClinPred

0.073

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

Varity_R

0.36

gMVP

0.39

Mutation Taster

=24/76

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over