Variant 11-28036256-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031217.4(KIF18A):c.2357A>T(p.Gln786Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

KIF18A
NM_031217.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.22

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.124990284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF18A	NM_031217.4 linkuse as main transcript	c.2357A>T	p.Gln786Leu	missense_variant	14/17	ENST00000263181.7	NP_112494.3	Q8NI77
KIF18A	XM_017018379.2 linkuse as main transcript	c.2357A>T	p.Gln786Leu	missense_variant	14/17		XP_016873868.1	Q8NI77
KIF18A	XM_017018380.2 linkuse as main transcript	c.1025A>T	p.Gln342Leu	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.2357A>T	p.Gln786Leu	missense_variant	14/17	1	NM_031217.4	ENSP00000263181.6		Q8NI77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455380

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723738

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 16, 2022

The c.2357A>T (p.Q786L) alteration is located in exon 14 (coding exon 13) of the KIF18A gene. This alteration results from a A to T substitution at nucleotide position 2357, causing the glutamine (Q) at amino acid position 786 to be replaced by a leucine (L). 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

0.081

BayesDel_addAF

Benign

-0.054

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

Eigen

Benign

-0.14

Eigen_PC

Benign

0.029

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.57

M_CAP

Benign

0.038

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.66

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.74

REVEL

Benign

0.081

Sift

Benign

0.030

Sift4G

Benign

0.29

Polyphen

0.16

Vest4

0.19

MutPred

0.087

Loss of ubiquitination at K782 (P = 0.2053);

MVP

0.76

MPC

0.14

ClinPred

0.54

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.34

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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