Genetic Variant KIFC2:c.*612_*614delCCT (chr8-144473998-GCTC-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001369769.2(KIFC2):c.*612_*614delCCT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 568,502 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00075 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

KIFC2
NM_001369769.2 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.903

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIFC2	NM_001369769.2 link	c.612_614delCCT		3_prime_UTR_variant	Exon 18 of 18	ENST00000645548.2	NP_001356698.1
FOXH1	NM_003923.3 link	c.237_239delGAG		3_prime_UTR_variant	Exon 3 of 3	ENST00000377317.5	NP_003914.1	O75593

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIFC2	ENST00000645548.2 link	c.612_614delCCT	3_prime_UTR_variant	Exon 18 of 18		NM_001369769.2	ENSP00000494595.1	A0A2R8YEU8
FOXH1	ENST00000377317 link	c.237_239delGAG	3_prime_UTR_variant	Exon 3 of 3	1	NM_003923.3	ENSP00000366534.4	O75593
KIFC2	ENST00000301332.3 link	c.551_553delCCT	3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000301332.2	Q96AC6-1
KIFC2	ENST00000643461.1 link	n.3445_3447delCCT	non_coding_transcript_exon_variant	Exon 17 of 17

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

115

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000426

Gnomad OTH

AF:

0.000956

GnomAD4 exome

AF:

0.00123

AC:

512

AN:

416164

Hom.:

AF XY:

0.00159

AC XY:

344

AN XY:

216762

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

12022

Gnomad4 AMR exome

AF:

0.00179

AC:

AN:

16738

Gnomad4 ASJ exome

AF:

0.00343

AC:

AN:

13122

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

29768

Gnomad4 SAS exome

AF:

0.00655

AC:

242

AN:

36940

Gnomad4 FIN exome

AF:

0.0000354

AC:

AN:

28276

Gnomad4 NFE exome

AF:

0.000601

AC:

152

AN:

252830

Gnomad4 Remaining exome

AF:

0.00118

AC:

AN:

24598

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000748

AC:

114

AN:

152338

Hom.:

Cov.:

AF XY:

0.00102

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000241

AC:

0.0000240512

AN:

0.0000240512

Gnomad4 AMR

AF:

0.00314

AC:

0.00313684

AN:

0.00313684

Gnomad4 ASJ

AF:

0.00230

AC:

0.00230415

AN:

0.00230415

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00518

AC:

0.00518027

AN:

0.00518027

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000426

AC:

0.000426195

AN:

0.000426195

Gnomad4 OTH

AF:

0.000946

AC:

0.000946074

AN:

0.000946074

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.000703

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Holoprosencephaly sequence

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=100/0

polymorphism

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