Genetic Variant KIFC2:c.*377C>A (chr8-144473766-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001369769.2(KIFC2):c.*377C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000775 in 398,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00076 ( 0 hom. )

Consequence

KIFC2
NM_001369769.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.671

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital heart malformation
Inheritance: Unknown Classification: LIMITED Submitted by: Laboratory for Molecular Medicine

FOXH1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 8-144473766-C-A is Benign according to our data. Variant chr8-144473766-C-A is described in ClinVar as Benign. ClinVar VariationId is 362270.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIFC2	NM_001369769.2	MANE Select	c.*377C>A	3_prime_UTR	Exon 18 of 18	NP_001356698.1	A0A2R8YEU8
FOXH1	NM_003923.3	MANE Select	c.*472G>T	3_prime_UTR	Exon 3 of 3	NP_003914.1	O75593
KIFC2	NM_145754.5		c.*316C>A	3_prime_UTR	Exon 17 of 17	NP_665697.1	Q96AC6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KIFC2	ENST00000645548.2	MANE Select	c.*377C>A	3_prime_UTR	Exon 18 of 18	ENSP00000494595.1	A0A2R8YEU8
FOXH1	ENST00000377317.5	TSL:1 MANE Select	c.*472G>T	3_prime_UTR	Exon 3 of 3	ENSP00000366534.4	O75593
KIFC2	ENST00000301332.3	TSL:1	c.*316C>A	3_prime_UTR	Exon 17 of 17	ENSP00000301332.2	Q96AC6-1

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00827

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000763

AC:

188

AN:

246332

Hom.:

Cov.:

AF XY:

0.000915

AC XY:

115

AN XY:

125716

show subpopulations

African (AFR)

AF:

0.00133

AC:

AN:

6790

American (AMR)

AF:

0.00108

AC:

AN:

8372

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

8976

East Asian (EAS)

AF:

0.0000579

AC:

AN:

17272

South Asian (SAS)

AF:

0.00656

AC:

AN:

14334

European-Finnish (FIN)

AF:

0.0000574

AC:

AN:

17436

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1296

European-Non Finnish (NFE)

AF:

0.000424

AC:

AN:

155576

Other (OTH)

AF:

0.000491

AC:

AN:

16280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.000794

AC:

121

AN:

152322

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

41570

American (AMR)

AF:

0.000458

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00828

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68026

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.000139

Hom.:

Bravo

AF:

0.000725

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Holoprosencephaly sequence (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.4

(source)

DANN

Benign

0.55

PhyloP100

-0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over