Variant 8-144466436-C-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001369769.2(KIFC2):c.17C>G(p.Ser6Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000884 in 1,357,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04

Variant links:

Genes affected

KIFC2 (HGNC:29530): (kinesin family member C2) Predicted to enable microtubule binding activity and microtubule motor activity. Predicted to be involved in microtubule-based movement and mitotic spindle assembly. Predicted to be located in cytoplasm. Predicted to be part of kinesin complex. Predicted to be active in microtubule cytoskeleton and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

KIFC2 links:

TMEM276 (HGNC:56235): (transmembrane protein 276)

TMEM276 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC2	NM_001369769.2 link	c.17C>G	p.Ser6Trp	missense_variant	1/18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIFC2	ENST00000645548.2 link	c.17C>G	p.Ser6Trp	missense_variant	1/18		NM_001369769.2	ENSP00000494595.1	A0A2R8YEU8
KIFC2	ENST00000301332.3 link	c.17C>G	p.Ser6Trp	missense_variant	1/17	1		ENSP00000301332.2	Q96AC6-1
KIFC2	ENST00000642354.1 link	c.17C>G	p.Ser6Trp	missense_variant	1/18			ENSP00000496539.1	A0A2R8Y870
KIFC2	ENST00000643461.1 link	n.394C>G		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes

AF:

0.00000667

AC:

AN:

149984

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000149

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000911

AC:

AN:

1207292

Hom.:

Cov.:

AF XY:

0.0000100

AC XY:

AN XY:

597730

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.0000113

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000667

AC:

AN:

149984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73202

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000149

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ExAC

AF:

0.0000768

AC:

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

Apr 17, 2024

The c.17C>G (p.S6W) alteration is located in exon 1 (coding exon 1) of the KIFC2 gene. This alteration results from a C to G substitution at nucleotide position 17, causing the serine (S) at amino acid position 6 to be replaced by a tryptophan (W). 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

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;.;T

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.83

T;T;T

M_CAP

Pathogenic

0.94

MetaRNN

Uncertain

0.52

D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.7

.;.;L

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-2.3

.;.;N

REVEL

Uncertain

0.57

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.65

MutPred

0.39

Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);Loss of disorder (P = 4e-04);

MVP

0.92

ClinPred

0.38

GERP RS

3.8

Varity_R

0.38

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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