1-44750466-T-C

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2

The NM_001297657.2(KIF2C):ā€‹c.2T>Cā€‹(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000257 in 1,558,226 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

KIF2C
NM_001297657.2 start_lost

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.33
Variant links:
Genes affected
KIF2C (HGNC:6393): (kinesin family member 2C) This gene encodes a kinesin-like protein that functions as a microtubule-dependent molecular motor. The encoded protein can depolymerize microtubules at the plus end, thereby promoting mitotic chromosome segregation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PVS1
Start lost variant, no new inframe start found.
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KIF2CNM_006845.4 linkc.341T>C p.Met114Thr missense_variant 5/21 ENST00000372224.9 NP_006836.2 Q99661-1A0A140VKF1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KIF2CENST00000372224.9 linkc.341T>C p.Met114Thr missense_variant 5/211 NM_006845.4 ENSP00000361298.4 Q99661-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00000213
AC:
3
AN:
1406010
Hom.:
0
Cov.:
30
AF XY:
0.00000286
AC XY:
2
AN XY:
699216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000405
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000126
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.26e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152216
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74370
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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

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 submitterclinical testingAmbry GeneticsDec 21, 2022The c.341T>C (p.M114T) alteration is located in exon 5 (coding exon 5) of the KIF2C gene. This alteration results from a T to C substitution at nucleotide position 341, causing the methionine (M) at amino acid position 114 to be replaced by a threonine (T). 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
0.31
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Uncertain
-0.080
CADD
Benign
21
DANN
Benign
0.97
DEOGEN2
Benign
0.020
T;T;T;.
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.067
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.74
T;T;T;T
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.5
.;L;.;.
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.1
N;N;N;N
REVEL
Benign
0.23
Sift
Benign
0.75
T;T;T;T
Sift4G
Benign
0.63
T;T;T;T
Polyphen
0.0, 0.23
.;B;.;B
Vest4
0.60, 0.60
MutPred
0.14
Gain of phosphorylation at M114 (P = 0.0211);Gain of phosphorylation at M114 (P = 0.0211);.;.;
MVP
0.82
MPC
0.43
ClinPred
0.50
D
GERP RS
5.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.096
gMVP
0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1649447974; hg19: chr1-45216138; API