Variant rs533812435 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_001098511.3(KIF2A):c.48G>A(p.Glu16Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000616 in 1,546,228 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00063 ( 2 hom. )

Consequence

KIF2A
NM_001098511.3 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.50

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 5-62306520-G-A is Benign according to our data. Variant chr5-62306520-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 435641.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1, Benign=1}.

BP7

Synonymous conserved (PhyloP=1.5 with no splicing effect.

BS2

High AC in GnomAd4 at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3 linkuse as main transcript	c.48G>A	p.Glu16Glu	synonymous_variant	1/21	ENST00000407818.8	NP_001091981.1	O00139-4
KIF2A	NM_004520.5 linkuse as main transcript	c.48G>A	p.Glu16Glu	synonymous_variant	1/20		NP_004511.2	O00139-3
KIF2A	NM_001243953.2 linkuse as main transcript	c.48G>A	p.Glu16Glu	synonymous_variant	1/20		NP_001230882.1	A0A6Q8PFA6B0AZS5
KIF2A	NM_001243952.2 linkuse as main transcript	c.-237G>A		5_prime_UTR_variant	1/21		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.48G>A	p.Glu16Glu	synonymous_variant	1/21	1	NM_001098511.3	ENSP00000385000.3		O00139-4
ENSG00000288643	ENST00000509663.2 linkuse as main transcript	n.48G>A		non_coding_transcript_exon_variant	1/6	3		ENSP00000502199.1		A0A6Q8PGD0

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000524

AC:

AN:

145060

Hom.:

AF XY:

0.000463

AC XY:

AN XY:

77738

show subpopulations

Gnomad AFR exome

AF:

0.000154

Gnomad AMR exome

AF:

0.00127

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000671

Gnomad OTH exome

AF:

0.000737

GnomAD4 exome

AF:

0.000626

AC:

872

AN:

1393916

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

406

AN XY:

687452

show subpopulations

Gnomad4 AFR exome

AF:

0.000130

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000283

Gnomad4 SAS exome

AF:

0.000281

Gnomad4 FIN exome

AF:

0.0000822

Gnomad4 NFE exome

AF:

0.000701

Gnomad4 OTH exome

AF:

0.000554

GnomAD4 genome

AF:

0.000525

AC:

AN:

152312

Hom.:

Cov.:

AF XY:

0.000591

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000573

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000573

Hom.:

Bravo

AF:

0.000752

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	KIF2A: BP4, BP7 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2020	- -

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 18, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.97

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