rs753498379

Variant names:

• chr8-144466436-C-A
• NM_001369769.2:c.17C>A

Your query was ambiguous. Multiple possible variants found:

• chr8-144466436-C-A
• chr8-144466436-C-G
• chr8-144466436-C-T

Variant summary

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

The NM_001369769.2(KIFC2):​c.17C>A​(p.Ser6*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000828 in 1,207,292 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 8.3e-7 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.04

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2	c.17C>A	p.Ser6*	stop_gained	Exon 1 of 18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIFC2	ENST00000645548.2	c.17C>A	p.Ser6*	stop_gained	Exon 1 of 18		NM_001369769.2	ENSP00000494595.1
KIFC2	ENST00000301332.3	c.17C>A	p.Ser6*	stop_gained	Exon 1 of 17	1		ENSP00000301332.2
KIFC2	ENST00000642354.1	c.17C>A	p.Ser6*	stop_gained	Exon 1 of 18			ENSP00000496539.1
KIFC2	ENST00000643461.1	n.394C>A		non_coding_transcript_exon_variant	Exon 1 of 17

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 8.28e-7 AC: 1 AN: 1207292 Hom.: 0 Cov.: 28 AF XY: 0.00000167 AC XY: 1 AN XY: 597730

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000416

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	43
DANN	Uncertain	0.99
Eigen	Uncertain	0.65
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.91	D
Vest4		0.096
GERP RS		3.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: chr8-145691819; COSMIC: COSV100023774; COSMIC: COSV100023774;