5-62306392-A-G

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.-81A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 326,330 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (3 hom., cov: 29)
  • Exomes 𝑓: 0.0091 (9 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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=-0.74).
• BP6: Variant 5-62306392-A-G is Benign according to our data. Variant chr5-62306392-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1210636.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 754 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.-81A>G		5_prime_UTR_variant	1/21	ENST00000407818.8
KIF2A	NM_001243952.2	c.-365A>G		5_prime_UTR_variant	1/21
KIF2A	NM_001243953.2	c.-81A>G		5_prime_UTR_variant	1/20
KIF2A	NM_004520.5	c.-81A>G		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.-81A>G		5_prime_UTR_variant	1/21	1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.00798 AC: 754 AN: 94438 Hom.: 3 Cov.: 29

Gnomad AFR AF: 0.00195

Gnomad AMI AF: 0.0361

Gnomad AMR AF: 0.00672

Gnomad ASJ AF: 0.00823

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00175

Gnomad FIN AF: 0.0234

Gnomad MID AF: 0.00481

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.00825

GnomAD4 exome AF: 0.00910 AC: 2110 AN: 231824 Hom.: 9 Cov.: 4 AF XY: 0.00881 AC XY: 1088 AN XY: 123534

Gnomad4 AFR exome AF: 0.000881

Gnomad4 AMR exome AF: 0.00763

Gnomad4 ASJ exome AF: 0.0106

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00253

Gnomad4 FIN exome AF: 0.0126

Gnomad4 NFE exome AF: 0.0107

Gnomad4 OTH exome AF: 0.00888

GnomAD4 genome AF: 0.00799 AC: 755 AN: 94506 Hom.: 3 Cov.: 29 AF XY: 0.00814 AC XY: 377 AN XY: 46338

Gnomad4 AFR AF: 0.00195

Gnomad4 AMR AF: 0.00671

Gnomad4 ASJ AF: 0.00823

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00209

Gnomad4 FIN AF: 0.0234

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.00818

Alfa AF: 0.00164 Hom.: 1

Bravo AF: 0.00473

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	15
Dann	Benign	0.78

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: rs563434700; hg19: chr5-61602219;