chr8-144467326-C-G

Variant names:

• chr8-144467326-C-G
• rs763870569
• NM_001369769.2:c.454C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001369769.2(KIFC2):​c.454C>G​(p.Pro152Ala) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P152L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 35)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07390642).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	NM_001369769.2	MANE Select	c.454C>G	p.Pro152Ala	missense	Exon 4 of 18	NP_001356698.1	A0A2R8YEU8
	KIFC2	NM_145754.5		c.454C>G	p.Pro152Ala	missense	Exon 4 of 17	NP_665697.1	Q96AC6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.454C>G	p.Pro152Ala	missense	Exon 4 of 18	ENSP00000494595.1	A0A2R8YEU8
	KIFC2	ENST00000301332.3	TSL:1	c.454C>G	p.Pro152Ala	missense	Exon 4 of 17	ENSP00000301332.2	Q96AC6-1
	KIFC2	ENST00000880943.1		c.454C>G	p.Pro152Ala	missense	Exon 4 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome Cov.: 66

GnomAD4 genome Cov.: 35

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.47
DANN	Benign	0.51
DEOGEN2	Benign	0.0081	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.3
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.057
Sift	Benign	0.042	D
Sift4G	Benign	0.49	T
Polyphen		0.0	B
Vest4		0.19
MutPred		0.16		Loss of catalytic residue at P152 (P = 0.0072)
MVP		0.29
ClinPred		0.041	T
GERP RS		-0.69
Varity_R		0.076
gMVP		0.25
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs763870569; hg19: chr8-145692709;