rs2275220

Positions:

• chr10-92612949-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004523.4(KIF11):​c.699-91A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 700,048 control chromosomes in the GnomAD database, including 639 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (138 hom., cov: 32)
  • Exomes 𝑓: 0.039 (501 hom.)
• Consequence: KIF11 NM_004523.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.306

Genes affected

KIF11 (HGNC:6388): (kinesin family member 11) This gene encodes a motor protein that belongs to the kinesin-like protein family. Members of this protein family are known to be involved in various kinds of spindle dynamics. The function of this gene product includes chromosome positioning, centrosome separation and establishing a bipolar spindle during cell mitosis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 10-92612949-A-G is Benign according to our data. Variant chr10-92612949-A-G is described in ClinVar as [Benign]. Clinvar id is 1245602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIF11	NM_004523.4	c.699-91A>G		intron_variant		ENST00000260731.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIF11	ENST00000260731.5	c.699-91A>G		intron_variant		1	NM_004523.4	P1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 5141 AN: 152084 Hom.: 138 Cov.: 32

Gnomad AFR AF: 0.00910

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0605

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.0308

Gnomad SAS AF: 0.0151

Gnomad FIN AF: 0.0815

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0225

GnomAD4 exome AF: 0.0392 AC: 21454 AN: 547846 Hom.: 501 AF XY: 0.0376 AC XY: 10848 AN XY: 288894

Gnomad4 AFR exome AF: 0.0100

Gnomad4 AMR exome AF: 0.0759

Gnomad4 ASJ exome AF: 0.0139

Gnomad4 EAS exome AF: 0.0252

Gnomad4 SAS exome AF: 0.0177

Gnomad4 FIN exome AF: 0.0792

Gnomad4 NFE exome AF: 0.0387

Gnomad4 OTH exome AF: 0.0349

GnomAD4 genome AF: 0.0338 AC: 5139 AN: 152202 Hom.: 138 Cov.: 32 AF XY: 0.0357 AC XY: 2655 AN XY: 74418

Gnomad4 AFR AF: 0.00908

Gnomad4 AMR AF: 0.0603

Gnomad4 ASJ AF: 0.0110

Gnomad4 EAS AF: 0.0307

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0815

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0223

Alfa AF: 0.0371 Hom.: 168

Bravo AF: 0.0305

Asia WGS AF: 0.0260 AC: 89 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.0
DANN	Benign	0.72

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: rs2275220; hg19: chr10-94372706; COSMIC: COSV53269446;