rs2297743

Variant names:

• chr10-92593066-C-G
• rs2297743
• ENST00000676647.1:c.-131+1237C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000676647.1(KIF11):​c.-131+1237C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,336 control chromosomes in the GnomAD database, including 1,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (1027 hom., cov: 33)
• Consequence: KIF11 ENST00000676647.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0740
• Publications: 3 publications found

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]

KIF11 Gene-Disease associations (from GenCC):

• ciliopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics
• microcephaly with or without chorioretinopathy, lymphedema, or intellectual disability

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-92593066-C-G is Benign according to our data. Variant chr10-92593066-C-G is described in ClinVar as Benign. ClinVar VariationId is 1289364.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000676647.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	NM_004523.4	MANE Select	c.-310C>G		upstream_gene	N/A	NP_004514.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIF11	ENST00000676647.1		c.-131+1237C>G		intron	N/A	ENSP00000503394.1	A0A7I2V3A9
	KIF11	ENST00000676757.1		c.-130-13199C>G		intron	N/A	ENSP00000504289.1	A0A7I2V3A9
	KIF11	ENST00000260731.5	TSL:1 MANE Select	c.-310C>G		upstream_gene	N/A	ENSP00000260731.3	P52732

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16173 AN: 152218 Hom.: 1022 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.0498

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0533

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0796

Gnomad OTH AF: 0.0917

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.106 AC: 16214 AN: 152336 Hom.: 1027 Cov.: 33 AF XY: 0.108 AC XY: 8014 AN XY: 74488

African (AFR) AF: 0.145 AC: 6011 AN: 41566

American (AMR) AF: 0.154 AC: 2361 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0498 AC: 173 AN: 3472

East Asian (EAS) AF: 0.128 AC: 661 AN: 5180

South Asian (SAS) AF: 0.165 AC: 795 AN: 4830

European-Finnish (FIN) AF: 0.0533 AC: 566 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0797 AC: 5421 AN: 68040

Other (OTH) AF: 0.0936 AC: 198 AN: 2116

Alfa AF: 0.0970 Hom.: 106

Bravo AF: 0.115

Asia WGS AF: 0.136 AC: 473 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	5.6
DANN	Benign	0.66
PhyloP100		-0.074
PromoterAI		0.043	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2297743; hg19: chr10-94352823;