8-144466436-C-G

Variant names:

• chr8-144466436-C-G
• rs753498379
• NM_001369769.2:c.17C>G

Variant summary

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

The NM_001369769.2(KIFC2):​c.17C>G​(p.Ser6Trp) variant causes a missense change. The variant allele was found at a frequency of 0.00000884 in 1,357,276 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000091 (0 hom.)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.04
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

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.17C>G	p.Ser6Trp	missense	Exon 1 of 18	NP_001356698.1	A0A2R8YEU8
	KIFC2	NM_145754.5		c.17C>G	p.Ser6Trp	missense	Exon 1 of 17	NP_665697.1	Q96AC6-1
	TMEM276	NM_001408061.1		c.-348G>C		5_prime_UTR	Exon 1 of 3	NP_001394990.1	P0DTL5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KIFC2	ENST00000645548.2	MANE Select	c.17C>G	p.Ser6Trp	missense	Exon 1 of 18	ENSP00000494595.1	A0A2R8YEU8
	KIFC2	ENST00000301332.3	TSL:1	c.17C>G	p.Ser6Trp	missense	Exon 1 of 17	ENSP00000301332.2	Q96AC6-1
	KIFC2	ENST00000880943.1		c.17C>G	p.Ser6Trp	missense	Exon 1 of 19	ENSP00000551002.1

Frequencies

GnomAD3 genomes AF: 0.00000667 AC: 1 AN: 149984 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000431 AC: 6 AN: 139194 AF XY: 0.0000499

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000919

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000911 AC: 11 AN: 1207292 Hom.: 0 Cov.: 28 AF XY: 0.0000100 AC XY: 6 AN XY: 597730

African (AFR) AF: 0.00 AC: 0 AN: 24062

American (AMR) AF: 0.00 AC: 0 AN: 22984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18028

East Asian (EAS) AF: 0.00 AC: 0 AN: 24036

South Asian (SAS) AF: 0.00 AC: 0 AN: 56204

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37684

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4626

European-Non Finnish (NFE) AF: 0.0000113 AC: 11 AN: 973778

Other (OTH) AF: 0.00 AC: 0 AN: 45890

GnomAD4 genome AF: 0.00000667 AC: 1 AN: 149984 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 73202

African (AFR) AF: 0.00 AC: 0 AN: 41132

American (AMR) AF: 0.00 AC: 0 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9884

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000149 AC: 1 AN: 67194

Other (OTH) AF: 0.00 AC: 0 AN: 2058

Alfa AF: 0.0000712 Hom.: 0

ExAC AF: 0.0000768 AC: 9

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.83	T
M_CAP	Pathogenic	0.94	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Benign	1.7	L
PhyloP100		5.0
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.57
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.65
MutPred		0.39		Loss of disorder (P = 4e-04)
MVP		0.92
ClinPred		0.38	T
GERP RS		3.8
PromoterAI		-0.036	Neutral
Varity_R		0.38
gMVP		0.84
Mutation Taster		=79/21	polymorphism

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

Other links and lift over

dbSNP: rs753498379; hg19: chr8-145691819;