chr8-144467234-C-G

Position:

• chr8-144467234-C-G

Variant summary

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

The NM_001369769.2(KIFC2):​c.362C>G​(p.Thr121Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 35)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.264

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]

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=0.1788699).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.362C>G	p.Thr121Ser	missense_variant	4/18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.362C>G	p.Thr121Ser	missense_variant	4/18		NM_001369769.2	ENSP00000494595.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 35

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

Oct 29, 2024

The c.362C>G (p.T121S) alteration is located in exon 4 (coding exon 4) of the KIFC2 gene. This alteration results from a C to G substitution at nucleotide position 362, causing the threonine (T) at amino acid position 121 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	0.27
BayesDel_addAF	Benign	-0.079	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	.;.;T
Eigen	Benign	-0.068
Eigen_PC	Benign	-0.084
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.65	T;T;T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.18	T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.1	.;.;L
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.31	.;.;N
REVEL	Benign	0.12
Sift	Pathogenic	0.0	.;.;D
Sift4G	Pathogenic	0.0	.;.;D
Polyphen		0.89	.;.;P
Vest4		0.43
MutPred		0.15		Gain of disorder (P = 0.0412);Gain of disorder (P = 0.0412);Gain of disorder (P = 0.0412);
MVP		0.74
ClinPred		0.88	D
GERP RS		3.8
Varity_R		0.26
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr8-145692617;