8-144467619-A-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001369769.2(KIFC2):c.604A>T(p.Ile202Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,593,904 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (34 hom.)
• Consequence: KIFC2 NM_001369769.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.621

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 Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0063176155).
• BP6: Variant 8-144467619-A-T is Benign according to our data. Variant chr8-144467619-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 2658987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC2	NM_001369769.2	c.604A>T	p.Ile202Phe	missense_variant	5/18	ENST00000645548.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIFC2	ENST00000645548.2	c.604A>T	p.Ile202Phe	missense_variant	5/18		NM_001369769.2	P1

Frequencies

GnomAD3 genomes AF: 0.00338 AC: 515 AN: 152182 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00123

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00609

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.00309 AC: 724 AN: 234294 Hom.: 2 AF XY: 0.00318 AC XY: 403 AN XY: 126582

Gnomad AFR exome AF: 0.00113

Gnomad AMR exome AF: 0.00126

Gnomad ASJ exome AF: 0.000357

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000757

Gnomad FIN exome AF: 0.000964

Gnomad NFE exome AF: 0.00570

Gnomad OTH exome AF: 0.00301

GnomAD4 exome AF: 0.00557 AC: 8028 AN: 1441604 Hom.: 34 Cov.: 35 AF XY: 0.00534 AC XY: 3824 AN XY: 715482

Gnomad4 AFR exome AF: 0.000640

Gnomad4 AMR exome AF: 0.00145

Gnomad4 ASJ exome AF: 0.000404

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000704

Gnomad4 FIN exome AF: 0.000785

Gnomad4 NFE exome AF: 0.00685

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.00337 AC: 514 AN: 152300 Hom.: 3 Cov.: 33 AF XY: 0.00306 AC XY: 228 AN XY: 74482

Gnomad4 AFR AF: 0.00123

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00609

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.00434 Hom.: 1

Bravo AF: 0.00356

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00623 AC: 24

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00640 AC: 55

ExAC AF: 0.00293 AC: 355

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

KIFC2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
Cadd	Benign	16
Dann	Uncertain	0.99
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.55	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.52	T
Polyphen		0.94	.;.;P
Vest4		0.50
MVP		0.53
ClinPred		0.022	T
GERP RS		3.5
Varity_R		0.17
gMVP		0.29

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: rs146924845; hg19: chr8-145693002; COSMIC: COSV100024110; COSMIC: COSV100024110;