5-62306436-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001098511.3(KIF2A):c.-37C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000219 in 1,523,636 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00022 (1 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.681

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 5-62306436-C-A is Benign according to our data. Variant chr5-62306436-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 512622.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 32 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.-37C>A		5_prime_UTR_variant	1/21	ENST00000407818.8
KIF2A	NM_001243952.2	c.-321C>A		5_prime_UTR_variant	1/21
KIF2A	NM_001243953.2	c.-37C>A		5_prime_UTR_variant	1/20
KIF2A	NM_004520.5	c.-37C>A		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.-37C>A		5_prime_UTR_variant	1/21	1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152132 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000228 AC: 31 AN: 135738 Hom.: 0 AF XY: 0.000164 AC XY: 12 AN XY: 73290

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000397

Gnomad ASJ exome AF: 0.00139

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000198

Gnomad OTH exome AF: 0.000260

GnomAD4 exome AF: 0.000219 AC: 301 AN: 1371396 Hom.: 1 Cov.: 25 AF XY: 0.000207 AC XY: 140 AN XY: 677304

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000347

Gnomad4 ASJ exome AF: 0.00158

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000226

Gnomad4 OTH exome AF: 0.000176

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152240 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74434

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.000214 Hom.: 0

Bravo AF: 0.000264

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 05, 2017

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Benign	0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs374889152; hg19: chr5-61602263;