chr1-44747691-C-T

Position:

• chr1-44747691-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006845.4(KIF2C):​c.307C>T​(p.Pro103Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KIF2C NM_006845.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.02

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]

KIF2C (HGNC:):

ACMG classification

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=0.22217637).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIF2C	NM_006845.4	c.307C>T	p.Pro103Ser	missense_variant	4/21	ENST00000372224.9	NP_006836.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIF2C	ENST00000372224.9	c.307C>T	p.Pro103Ser	missense_variant	4/21	1	NM_006845.4	ENSP00000361298.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2024

The c.307C>T (p.P103S) alteration is located in exon 4 (coding exon 4) of the KIF2C gene. This alteration results from a C to T substitution at nucleotide position 307, causing the proline (P) at amino acid position 103 to be replaced by a serine (S). 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	0.33
BayesDel_addAF	Uncertain	0.067	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.053	T;T;T;.
Eigen	Benign	0.034
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	1.6	.;L;.;.
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.3	D;D;D;D
REVEL	Benign	0.17
Sift	Benign	0.075	T;T;D;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.0050, 0.0030	.;B;.;B
Vest4		0.32, 0.46
MutPred		0.22		Gain of phosphorylation at P103 (P = 0.0104);Gain of phosphorylation at P103 (P = 0.0104);.;.;
MVP		0.69
MPC		0.95
ClinPred		0.95	D
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-45213363;