Variant 11-28021252-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_031217.4(KIF18A):c.2645C>T(p.Pro882Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,488,032 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

KIF18A
NM_031217.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.02

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004211366).

BP6

Variant 11-28021252-G-A is Benign according to our data. Variant chr11-28021252-G-A is described in ClinVar as [Benign]. Clinvar id is 720712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 420 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF18A	NM_031217.4 linkuse as main transcript	c.2645C>T	p.Pro882Leu	missense_variant	17/17	ENST00000263181.7	NP_112494.3	Q8NI77
KIF18A	XM_017018379.2 linkuse as main transcript	c.2645C>T	p.Pro882Leu	missense_variant	17/17		XP_016873868.1	Q8NI77
KIF18A	XM_017018380.2 linkuse as main transcript	c.1313C>T	p.Pro438Leu	missense_variant	9/9		XP_016873869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF18A	ENST00000263181.7 linkuse as main transcript	c.2645C>T	p.Pro882Leu	missense_variant	17/17	1	NM_031217.4	ENSP00000263181.6		Q8NI77

Frequencies

GnomAD3 genomes

AF:

0.00275

AC:

418

AN:

151866

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00929

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000536

AC:

AN:

149322

Hom.:

AF XY:

0.000411

AC XY:

AN XY:

80248

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.000367

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000317

Gnomad OTH exome

AF:

0.000541

GnomAD4 exome

AF:

0.000246

AC:

328

AN:

1336048

Hom.:

Cov.:

AF XY:

0.000237

AC XY:

156

AN XY:

659498

show subpopulations

Gnomad4 AFR exome

AF:

0.00942

Gnomad4 AMR exome

AF:

0.000340

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000140

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000115

Gnomad4 OTH exome

AF:

0.000583

GnomAD4 genome

AF:

0.00276

AC:

420

AN:

151984

Hom.:

Cov.:

AF XY:

0.00261

AC XY:

194

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00931

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000420

Hom.:

Bravo

AF:

0.00333

ESP6500AA

AF:

0.00855

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000622

AC:

Asia WGS

AF:

0.000870

AC:

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 25, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.014

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0042

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.064

Sift

Benign

0.093

Sift4G

Benign

0.15

Polyphen

0.0010

Vest4

0.10

MVP

0.75

MPC

0.11

ClinPred

0.0096

GERP RS

2.7

Varity_R

0.025

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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