11-28036487-T-C

Position:

• chr11-28036487-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000263181.7(KIF18A):​c.2126A>G​(p.Asp709Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: KIF18A ENST00000263181.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

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=0.08867094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF18A	NM_031217.4	c.2126A>G	p.Asp709Gly	missense_variant	14/17	ENST00000263181.7	NP_112494.3
KIF18A	XM_017018379.2	c.2126A>G	p.Asp709Gly	missense_variant	14/17		XP_016873868.1
KIF18A	XM_017018380.2	c.794A>G	p.Asp265Gly	missense_variant	6/9		XP_016873869.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF18A	ENST00000263181.7	c.2126A>G	p.Asp709Gly	missense_variant	14/17	1	NM_031217.4	ENSP00000263181	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.2126A>G (p.D709G) alteration is located in exon 14 (coding exon 13) of the KIF18A gene. This alteration results from a A to G substitution at nucleotide position 2126, causing the aspartic acid (D) at amino acid position 709 to be replaced by a glycine (G). 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	0.10
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.69	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	0.73	D
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.19	N
REVEL	Benign	0.13
Sift	Benign	0.066	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.19		Loss of helix (P = 0.0626);
MVP		0.74
MPC		0.15
ClinPred		0.15	T
GERP RS		4.7
Varity_R		0.10
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-28058034;