Variant 8-144466443-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001369769.2(KIFC2):c.24C>T(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,363,372 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0016 ( 29 hom. )

Consequence

KIFC2
NM_001369769.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0820

Variant links:

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]

KIFC2 links:

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

TMEM276 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant 8-144466443-C-T is Benign according to our data. Variant chr8-144466443-C-T is described in ClinVar as [Benign]. Clinvar id is 782144.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.082 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00278 (417/150082) while in subpopulation SAS AF= 0.0193 (93/4814). AF 95% confidence interval is 0.0161. There are 1 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 29 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIFC2	NM_001369769.2 link	c.24C>T	p.Leu8Leu	synonymous_variant	1/18	ENST00000645548.2	NP_001356698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KIFC2	ENST00000645548.2 link	c.24C>T	p.Leu8Leu	synonymous_variant	1/18		NM_001369769.2	ENSP00000494595.1	A0A2R8YEU8
KIFC2	ENST00000301332.3 link	c.24C>T	p.Leu8Leu	synonymous_variant	1/17	1		ENSP00000301332.2	Q96AC6-1
KIFC2	ENST00000642354.1 link	c.24C>T	p.Leu8Leu	synonymous_variant	1/18			ENSP00000496539.1	A0A2R8Y870
KIFC2	ENST00000643461.1 link	n.401C>T		non_coding_transcript_exon_variant	1/17

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

408

AN:

149974

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00384

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00216

Gnomad SAS

AF:

0.0191

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.000670

Gnomad OTH

AF:

0.00436

GnomAD3 exomes

AF:

0.00350

AC:

488

AN:

139430

Hom.:

AF XY:

0.00434

AC XY:

349

AN XY:

80352

show subpopulations

Gnomad AFR exome

AF:

0.00280

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000146

Gnomad EAS exome

AF:

0.000150

Gnomad SAS exome

AF:

0.0201

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000673

Gnomad OTH exome

AF:

0.00336

GnomAD4 exome

AF:

0.00159

AC:

1933

AN:

1213290

Hom.:

Cov.:

AF XY:

0.00190

AC XY:

1140

AN XY:

600682

show subpopulations

Gnomad4 AFR exome

AF:

0.00463

Gnomad4 AMR exome

AF:

0.00163

Gnomad4 ASJ exome

AF:

0.000110

Gnomad4 EAS exome

AF:

0.00246

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.0000263

Gnomad4 NFE exome

AF:

0.000487

Gnomad4 OTH exome

AF:

0.00286

GnomAD4 genome

AF:

0.00278

AC:

417

AN:

150082

Hom.:

Cov.:

AF XY:

0.00304

AC XY:

223

AN XY:

73310

show subpopulations

Gnomad4 AFR

AF:

0.00458

Gnomad4 AMR

AF:

0.00383

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00217

Gnomad4 SAS

AF:

0.0193

Gnomad4 FIN

AF:

0.000101

Gnomad4 NFE

AF:

0.000670

Gnomad4 OTH

AF:

0.00671

Alfa

AF:

0.000156

Hom.:

Asia WGS

AF:

0.0180

AC:

AN:

3172

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 28, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over