Variant 8-144466461-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001369769.2(KIFC2):c.42C>A(p.Ser14Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,362,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 31)

Exomes 𝑓: 8.2e-7 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.427

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:):

TMEM276 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32067722).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC2	NM_001369769.2 linkuse as main transcript	c.42C>A	p.Ser14Arg	missense_variant	1/18	ENST00000645548.2
TMEM276	NM_001408062.1 linkuse as main transcript	c.-196+492G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFC2	ENST00000645548.2 linkuse as main transcript	c.42C>A	p.Ser14Arg	missense_variant	1/18		NM_001369769.2	P1
KIFC2	ENST00000301332.3 linkuse as main transcript	c.42C>A	p.Ser14Arg	missense_variant	1/17	1			Q96AC6-1
KIFC2	ENST00000642354.1 linkuse as main transcript	c.42C>A	p.Ser14Arg	missense_variant	1/18
KIFC2	ENST00000643461.1 linkuse as main transcript	n.419C>A		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes

AF:

0.00000666

AC:

AN:

150058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

8.25e-7

AC:

AN:

1212144

Hom.:

Cov.:

AF XY:

0.00000167

AC XY:

AN XY:

599178

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:

0.00000102

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000666

AC:

AN:

150058

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73228

show subpopulations

Gnomad4 AFR

AF:

0.0000243

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Sep 13, 2023

The c.42C>A (p.S14R) alteration is located in exon 1 (coding exon 1) of the KIFC2 gene. This alteration results from a C to A substitution at nucleotide position 42, causing the serine (S) at amino acid position 14 to be replaced by an arginine (R). 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

0.95

BayesDel_addAF

Uncertain

0.012

BayesDel_noAF

Benign

-0.22

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.68

T;T;T

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.88

PrimateAI

Pathogenic

0.92

Polyphen

0.94

.;.;P

Vest4

0.64

MutPred

0.29

Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);Gain of MoRF binding (P = 0.0072);

MVP

0.74

ClinPred

0.90

GERP RS

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.63

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