Variant 11-28036505-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000263181.7(KIF18A):c.2108T>C(p.Ile703Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000298 in 1,611,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

KIF18A
ENST00000263181.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

Variant links:

Genes affected

KIF18A (HGNC:29441): (kinesin family member 18A) KIF18A is a member of the kinesin superfamily of microtubule-associated molecular motors (see MIM 148760) that use hydrolysis of ATP to produce force and movement along microtubules (Luboshits and Benayahu, 2005 [PubMed 15878648]).[supplied by OMIM, Aug 2008]

KIF18A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2571199).

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KIF18A	NM_031217.4 linkuse as main transcript	c.2108T>C	p.Ile703Thr	missense_variant	14/17	ENST00000263181.7	NP_112494.3
KIF18A	XM_017018379.2 linkuse as main transcript	c.2108T>C	p.Ile703Thr	missense_variant	14/17		XP_016873868.1
KIF18A	XM_017018380.2 linkuse as main transcript	c.776T>C	p.Ile259Thr	missense_variant	6/9		XP_016873869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF18A	ENST00000263181.7 linkuse as main transcript	c.2108T>C	p.Ile703Thr	missense_variant	14/17	1	NM_031217.4	ENSP00000263181	P1

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

151492

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000363

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.000482

GnomAD3 exomes

AF:

0.0000240

AC:

AN:

249738

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134974

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000192

AC:

AN:

1459746

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726196

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.000365

GnomAD4 genome

AF:

0.000132

AC:

AN:

151492

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

AN XY:

73982

show subpopulations

Gnomad4 AFR

AF:

0.000363

Gnomad4 AMR

AF:

0.000132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.000482

Alfa

AF:

0.000285

Hom.:

Bravo

AF:

0.000132

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 17, 2023

The c.2108T>C (p.I703T) alteration is located in exon 14 (coding exon 13) of the KIF18A gene. This alteration results from a T to C substitution at nucleotide position 2108, causing the isoleucine (I) at amino acid position 703 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.050

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.40

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.83

M_CAP

Benign

0.072

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.78

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.76

REVEL

Uncertain

0.32

Sift

Uncertain

0.0030

Sift4G

Benign

0.64

Polyphen

0.10

Vest4

0.55

MVP

0.71

MPC

0.25

ClinPred

0.098

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.097

gMVP

0.45

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over