5-62306223-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001098511.3(KIF2A):c.-250C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0682 in 459,908 control chromosomes in the GnomAD database, including 1,418 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (436 hom., cov: 33)
  • Exomes 𝑓: 0.072 (982 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.298

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-62306223-C-T is Benign according to our data. Variant chr5-62306223-C-T is described in ClinVar as [Benign]. Clinvar id is 1222402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF2A	NM_001098511.3	c.-250C>T		5_prime_UTR_variant	1/21	ENST00000407818.8
KIF2A	NM_001243952.2	c.-534C>T		5_prime_UTR_variant	1/21
KIF2A	NM_001243953.2	c.-250C>T		5_prime_UTR_variant	1/20
KIF2A	NM_004520.5	c.-250C>T		5_prime_UTR_variant	1/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF2A	ENST00000407818.8	c.-250C>T		5_prime_UTR_variant	1/21	1	NM_001098511.3	A1

Frequencies

GnomAD3 genomes AF: 0.0608 AC: 9240 AN: 152086 Hom.: 436 Cov.: 33

Gnomad AFR AF: 0.0141

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.0717

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.000580

Gnomad SAS AF: 0.0285

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0722

GnomAD4 exome AF: 0.0718 AC: 22102 AN: 307714 Hom.: 982 Cov.: 0 AF XY: 0.0706 AC XY: 11440 AN XY: 161926

Gnomad4 AFR exome AF: 0.0163

Gnomad4 AMR exome AF: 0.0661

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.0000482

Gnomad4 SAS exome AF: 0.0356

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.0786

GnomAD4 genome AF: 0.0607 AC: 9241 AN: 152194 Hom.: 436 Cov.: 33 AF XY: 0.0591 AC XY: 4396 AN XY: 74400

Gnomad4 AFR AF: 0.0140

Gnomad4 AMR AF: 0.0718

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.000582

Gnomad4 SAS AF: 0.0286

Gnomad4 FIN AF: 0.0617

Gnomad4 NFE AF: 0.0854

Gnomad4 OTH AF: 0.0710

Alfa AF: 0.0276 Hom.: 16

Bravo AF: 0.0607

Asia WGS AF: 0.0190 AC: 64 AN: 3456

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	15
Dann	Benign	0.80

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: rs141968809; hg19: chr5-61602050;