8-144474164-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001369769.2(KIFC2):c.*775C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000612 in 1,200,052 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

KIFC2
NM_001369769.2 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0160

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:

FOXH1 (HGNC:3814): (forkhead box H1) FOXH1 encodes a human homolog of Xenopus forkhead activin signal transducer-1. FOXH1 protein binds SMAD2 and activates an activin response element via binding the DNA motif TGT(G/T)(T/G)ATT. [provided by RefSeq, Jul 2008]

FOXH1 links:

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ACMG classification

Classification made for transcript

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 (BayesDel_noAF=-0.77).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KIFC2	NM_001369769.2 linkuse as main transcript	c.*775C>T		3_prime_UTR_variant	18/18	ENST00000645548.2
FOXH1	NM_003923.3 linkuse as main transcript	c.*74G>A		3_prime_UTR_variant	3/3	ENST00000377317.5

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FOXH1	ENST00000377317.5 linkuse as main transcript	c.*74G>A	3_prime_UTR_variant	3/3	1	NM_003923.3	P1
KIFC2	ENST00000645548.2 linkuse as main transcript	c.*775C>T	3_prime_UTR_variant	18/18		NM_001369769.2	P1
KIFC2	ENST00000643461.1 linkuse as main transcript	n.3608C>T	non_coding_transcript_exon_variant	17/17
KIFC2	ENST00000301332.3 linkuse as main transcript		downstream_gene_variant		1			Q96AC6-1

Frequencies

GnomAD3 genomes

AF:

0.000697

AC:

106

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.000958

GnomAD4 exome

AF:

0.000599

AC:

628

AN:

1047754

Hom.:

Cov.:

AF XY:

0.000608

AC XY:

316

AN XY:

519750

show subpopulations

Gnomad4 AFR exome

AF:

0.0000840

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.0000573

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000167

Gnomad4 FIN exome

AF:

0.0000476

Gnomad4 NFE exome

AF:

0.000680

Gnomad4 OTH exome

AF:

0.000769

GnomAD4 genome

AF:

0.000696

AC:

106

AN:

152298

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000192

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000832

Hom.:

Bravo

AF:

0.00102

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Holoprosencephaly sequence

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

1.7

Dann

Benign

0.55

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

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