5-62306211-A-C

Position:

• chr5-62306211-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001098511.3(KIF2A):​c.-262A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 436,982 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0071 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00074 (4 hom.)
• Consequence: KIF2A NM_001098511.3 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.100

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]

ENSG00000288643 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-62306211-A-C is Benign according to our data. Variant chr5-62306211-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1190889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00708 (1072/151328) while in subpopulation AFR AF= 0.024 (989/41168). AF 95% confidence interval is 0.0228. There are 6 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1072 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2A	NM_001098511.3	c.-262A>C		5_prime_UTR_variant	1/21	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5	c.-262A>C		5_prime_UTR_variant	1/20		NP_004511.2
KIF2A	NM_001243953.2	c.-262A>C		5_prime_UTR_variant	1/20		NP_001230882.1
KIF2A	NM_001243952.2	c.-546A>C		5_prime_UTR_variant	1/21		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818	c.-262A>C		5_prime_UTR_variant	1/21	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2	n.-262A>C		non_coding_transcript_exon_variant	1/6	3		ENSP00000502199.1
ENSG00000288643	ENST00000509663.2	n.-262A>C		5_prime_UTR_variant	1/6	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes AF: 0.00708 AC: 1070 AN: 151218 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00413

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00575

GnomAD4 exome AF: 0.000735 AC: 210 AN: 285654 Hom.: 4 Cov.: 0 AF XY: 0.000591 AC XY: 89 AN XY: 150518

Gnomad4 AFR exome AF: 0.0237

Gnomad4 AMR exome AF: 0.00355

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000119

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000560

Gnomad4 OTH exome AF: 0.00219

GnomAD4 genome AF: 0.00708 AC: 1072 AN: 151328 Hom.: 6 Cov.: 33 AF XY: 0.00665 AC XY: 492 AN XY: 73954

Gnomad4 AFR AF: 0.0240

Gnomad4 AMR AF: 0.00413

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00576 Hom.: 0

Bravo AF: 0.00825

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

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	14
DANN	Benign	0.81

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: rs181824384; hg19: chr5-61602038;