NM_001098511.3:c.961C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM2PM5PP3

The NM_001098511.3(KIF2A):c.961C>T(p.His321Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000693 in 1,442,740 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H321D) has been classified as Pathogenic.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF2A
NM_001098511.3 missense, splice_region

Scores

Splicing: ADA: 0.9967

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.91

Publications

10 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr5-62361330-C-G is described in ClinVar as [Pathogenic]. Clinvar id is 65400.Status of the report is no_assertion_criteria_provided, 0 stars.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF2A	NM_001098511.3 link	c.961C>T	p.His321Tyr	missense_variant, splice_region_variant	Exon 10 of 21	ENST00000407818.8	NP_001091981.1	O00139-4
KIF2A	NM_004520.5 link	c.961C>T	p.His321Tyr	missense_variant, splice_region_variant	Exon 10 of 20		NP_004511.2	O00139-3
KIF2A	NM_001243953.2 link	c.904C>T	p.His302Tyr	missense_variant, splice_region_variant	Exon 10 of 20		NP_001230882.1	A0A6Q8PFA6B0AZS5
KIF2A	NM_001243952.2 link	c.880C>T	p.His294Tyr	missense_variant, splice_region_variant	Exon 11 of 21		NP_001230881.2	O00139-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8 link	c.961C>T	p.His321Tyr	missense_variant, splice_region_variant	Exon 10 of 21	1	NM_001098511.3	ENSP00000385000.3		O00139-4
ENSG00000288643	ENST00000509663.2 link	n.64+54794C>T		intron_variant	Intron 1 of 5	3		ENSP00000502199.1		A0A6Q8PGD0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000419

AC:

AN:

238432

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000301

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:

0.00

GnomAD4 exome

AF:

6.93e-7

AC:

AN:

1442740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33132

American (AMR)

AF:

0.0000228

AC:

AN:

43798

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25856

East Asian (EAS)

AF:

0.00

AC:

AN:

39368

South Asian (SAS)

AF:

0.00

AC:

AN:

85000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1096986

Other (OTH)

AF:

0.00

AC:

AN:

59726

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.55

D;.;.;.;T

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.61

T;T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.70

D;D;D;D;D

MetaSVM

Benign

-0.60

MutationAssessor

Benign

-0.47

N;.;N;.;.

PhyloP100

7.9

PrimateAI

Pathogenic

0.93

PROVEAN

Pathogenic

-5.3

D;D;D;D;N

REVEL

Uncertain

0.59

Sift

Benign

0.087

T;T;T;T;D

Sift4G

Uncertain

0.050

T;T;D;D;D

Polyphen

0.60

P;.;B;.;.

Vest4

0.78

MutPred

0.65

Loss of catalytic residue at M323 (P = 0.0417);.;Loss of catalytic residue at M323 (P = 0.0417);.;.;

MVP

0.80

MPC

1.1

ClinPred

0.95

GERP RS

5.2

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.80

gMVP

0.87

Mutation Taster

=7/93

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over