8-144467530-C-A

Variant names:

• chr8-144467530-C-A
• rs770837004
• NM_001369769.2:c.515C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001369769.2(KIFC2):​c.515C>A​(p.Pro172Gln) 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. 15/20 in silico tools predict 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: 33)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.07

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05972466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.515C>A	p.Pro172Gln	missense_variant	Exon 5 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.515C>A	p.Pro172Gln	missense_variant	Exon 5 of 18		NM_001369769.2	ENSP00000494595.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.071
DANN	Benign	0.56
DEOGEN2	Benign	0.0021	.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.44	T;T;T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;.;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	1.3	.;.;N
REVEL	Benign	0.033
Sift	Benign	0.17	.;.;T
Sift4G	Benign	0.40	.;.;T
Polyphen		0.0040	.;.;B
Vest4		0.15
MutPred		0.070		Loss of glycosylation at T169 (P = 0.0817);Loss of glycosylation at T169 (P = 0.0817);Loss of glycosylation at T169 (P = 0.0817);
MVP		0.29
ClinPred		0.034	T
GERP RS		-1.6
Varity_R		0.071
gMVP		0.18

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

Other links and lift over

dbSNP: rs770837004; hg19: chr8-145692913;