Variant 8-144466474-G-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_001369769.2(KIFC2):c.55G>A(p.Asp19Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000245 in 1,346,022 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 0.000053 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.62

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12995547).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC2	NM_001369769.2 link	c.55G>A	p.Asp19Asn	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.55G>A	p.Asp19Asn	missense_variant	1/18		NM_001369769.2	ENSP00000494595.1	A0A2R8YEU8
KIFC2	ENST00000301332.3 link	c.55G>A	p.Asp19Asn	missense_variant	1/17	1		ENSP00000301332.2	Q96AC6-1
KIFC2	ENST00000642354.1 link	c.55G>A	p.Asp19Asn	missense_variant	1/18			ENSP00000496539.1	A0A2R8Y870
KIFC2	ENST00000643461.1 link	n.432G>A		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes

AF:

0.0000533

AC:

AN:

150160

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:

0.000981

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000424

AC:

AN:

117792

Hom.:

AF XY:

0.0000583

AC XY:

AN XY:

68628

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000985

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000209

AC:

AN:

1195754

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

589652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000366

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000218

GnomAD4 genome

AF:

0.0000532

AC:

AN:

150268

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

73408

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000984

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000446

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.0000260

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

Nov 21, 2024

The c.55G>A (p.D19N) alteration is located in exon 1 (coding exon 1) of the KIFC2 gene. This alteration results from a G to A substitution at nucleotide position 55, causing the aspartic acid (D) at amino acid position 19 to be replaced by an asparagine (N). 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

Uncertain

0.43

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0068

.;.;T

Eigen

Uncertain

0.29

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.75

T;T;T

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.32

MutationAssessor

Benign

1.7

.;.;L

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.88

.;.;N

REVEL

Benign

0.26

Sift

Pathogenic

0.0

.;.;D

Sift4G

Pathogenic

0.0

.;.;D

Polyphen

1.0

.;.;D

Vest4

0.25

MutPred

0.34

Gain of MoRF binding (P = 0.0564);Gain of MoRF binding (P = 0.0564);Gain of MoRF binding (P = 0.0564);

MVP

0.83

ClinPred

0.30

GERP RS

3.8

Varity_R

0.26

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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