8-144467230-G-C

Variant names:

• chr8-144467230-G-C
• rs775755787
• NM_001369769.2:c.358G>C

Variant summary

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

The NM_001369769.2(KIFC2):​c.358G>C​(p.Val120Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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: 35)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.21

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]

TMEM276 (HGNC:56235): (transmembrane protein 276)

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=0.0586372).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.358G>C	p.Val120Leu	missense_variant	Exon 4 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.358G>C	p.Val120Leu	missense_variant	Exon 4 of 18		NM_001369769.2	ENSP00000494595.1

Frequencies

GnomAD3 genomes Cov.: 35

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461332 Hom.: 0 Cov.: 65 AF XY: 0.00000275 AC XY: 2 AN XY: 726962

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 35

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0063	.;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.68	T;T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.059	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	.;.;N
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.29	.;.;N
REVEL	Benign	0.019
Sift	Benign	0.14	.;.;T
Sift4G	Benign	0.28	.;.;T
Polyphen		0.0010	.;.;B
Vest4		0.28
MutPred		0.15		Gain of disorder (P = 0.0923);Gain of disorder (P = 0.0923);Gain of disorder (P = 0.0923);
MVP		0.39
ClinPred		0.094	T
GERP RS		-0.30
Varity_R		0.075
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs775755787; hg19: chr8-145692613;