Genetic Variant KIFC2:p.Ala60Val (chr8-144466959-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001369769.2(KIFC2):c.179C>T(p.Ala60Val) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000027 in 1,592,080 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 missense, splice_region

Scores

Splicing: ADA: 0.0008066

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.56

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047153085).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001369769.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIFC2	NM_001369769.2	MANE Select	c.179C>T	p.Ala60Val	missense splice_region	Exon 3 of 18	NP_001356698.1	A0A2R8YEU8
KIFC2	NM_145754.5		c.179C>T	p.Ala60Val	missense splice_region	Exon 3 of 17	NP_665697.1	Q96AC6-1
TMEM276	NM_001408062.1		c.-202G>A		5_prime_UTR	Exon 1 of 3	NP_001394991.1	P0DTL5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KIFC2	ENST00000645548.2	MANE Select	c.179C>T	p.Ala60Val	missense splice_region	Exon 3 of 18	ENSP00000494595.1	A0A2R8YEU8
KIFC2	ENST00000301332.3	TSL:1	c.179C>T	p.Ala60Val	missense splice_region	Exon 3 of 17	ENSP00000301332.2	Q96AC6-1
KIFC2	ENST00000880943.1		c.179C>T	p.Ala60Val	missense splice_region	Exon 3 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152198

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:

0.000580

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

GnomAD2 exomes

AF:

0.0000945

AC:

AN:

211536

AF XY:

0.0000762

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000278

AC:

AN:

1439764

Hom.:

Cov.:

AF XY:

0.0000251

AC XY:

AN XY:

716010

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33150

American (AMR)

AF:

0.00

AC:

AN:

43866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25710

East Asian (EAS)

AF:

0.000941

AC:

AN:

39312

South Asian (SAS)

AF:

0.00

AC:

AN:

85054

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39424

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5562

European-Non Finnish (NFE)

AF:

9.03e-7

AC:

AN:

1107940

Other (OTH)

AF:

0.0000167

AC:

AN:

59746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152316

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41582

American (AMR)

AF:

0.00

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

ExAC

AF:

0.0000425

AC:

Asia WGS

AF:

0.000867

AC:

AN:

3476

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0061

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.85

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.64

M_CAP

Benign

0.021

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

2.6

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.81

REVEL

Benign

0.087

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.15

Vest4

0.21

MutPred

0.049

Gain of glycosylation at S62 (P = 0.1921)

MVP

0.40

ClinPred

0.096

GERP RS

0.99

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.076

gMVP

0.18

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00081

dbscSNV1_RF

Benign

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over