rs533812435

chr5-62306520-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001098511.3(KIF2A):c.48G>A(p.Glu16=) 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
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 1.50

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]

ACMG classification

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: {Benign=1, Uncertain_significance=1, Likely_benign=2}.
• BP7: Synonymous conserved (PhyloP=1.5 with no splicing effect.
• BS2: High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.48G>A	p.Glu16=	synonymous_variant	1/21	ENST00000407818.8
KIF2A	NM_004520.5	c.48G>A	p.Glu16=	synonymous_variant	1/20
KIF2A	NM_001243953.2	c.48G>A	p.Glu16=	synonymous_variant	1/20
KIF2A	NM_001243952.2	c.-237G>A		5_prime_UTR_variant	1/21

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.48G>A	p.Glu16=	synonymous_variant	1/21	1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152204 Hom.: 0 Cov.: 33

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: 76 AN: 145060 Hom.: 1 AF XY: 0.000463 AC XY: 36 AN XY: 77738

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.: 2 Cov.: 32 AF XY: 0.000591 AC XY: 406 AN XY: 687452

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: 80 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44 AN XY: 74478

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.: 0

Bravo AF: 0.000752

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Feb 01, 2023	KIF2A: BP4, BP7 -
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	12
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

Other links and lift over

dbSNP: rs533812435; hg19: chr5-61602347;