rs9672296

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_198525.3(KIF7):c.2896-14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 1,542,734 control chromosomes in the GnomAD database, including 246,102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.53 ( 21740 hom., cov: 33)

Exomes 𝑓: 0.56 ( 224362 hom. )

Consequence

KIF7
NM_198525.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -0.908

Publications

10 publications found

Variant links:

Genes affected

KIF7 (HGNC:30497): (kinesin family member 7) This gene encodes a cilia-associated protein belonging to the kinesin family. This protein plays a role in the sonic hedgehog (SHH) signaling pathway through the regulation of GLI transcription factors. It functions as a negative regulator of the SHH pathway by preventing inappropriate activation of GLI2 in the absence of ligand, and as a positive regulator by preventing the processing of GLI3 into its repressor form. Mutations in this gene have been associated with various ciliopathies. [provided by RefSeq, Oct 2011]

KIF7 Gene-Disease associations (from GenCC):

acrocallosal syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
neurodevelopmental disorder
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
hydrolethalus syndrome 2
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hydrolethalus syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
multiple epiphyseal dysplasia, Al-Gazali type
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
orofaciodigital syndrome type 6
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

KIF7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 15-89631724-C-T is Benign according to our data. Variant chr15-89631724-C-T is described in ClinVar as Benign. ClinVar VariationId is 96652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.2896-14G>A		intron_variant	Intron 14 of 18	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIF7	ENST00000394412.8 link	c.2896-14G>A	intron_variant	Intron 14 of 18	5	NM_198525.3	ENSP00000377934.3	Q2M1P5
KIF7	ENST00000696512.1 link	c.3019-14G>A	intron_variant	Intron 14 of 18			ENSP00000512678.1	A0A8Q3SIQ8
KIF7	ENST00000677187.1 link	n.570-14G>A	intron_variant	Intron 2 of 6

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

80743

AN:

151958

Hom.:

21721

Cov.:

show subpopulations

Gnomad AFR

AF:

0.483

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.478

Gnomad FIN

AF:

0.613

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.583

Gnomad OTH

AF:

0.513

GnomAD2 exomes

AF:

0.513

AC:

76741

AN:

149570

AF XY:

0.516

show subpopulations

Gnomad AFR exome

AF:

0.482

Gnomad AMR exome

AF:

0.418

Gnomad ASJ exome

AF:

0.531

Gnomad EAS exome

AF:

0.318

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.578

Gnomad OTH exome

AF:

0.511

GnomAD4 exome

AF:

0.564

AC:

784976

AN:

1390656

Hom.:

224362

Cov.:

AF XY:

0.563

AC XY:

385357

AN XY:

684902

show subpopulations

African (AFR)

AF:

0.478

AC:

15019

AN:

31422

American (AMR)

AF:

0.422

AC:

14914

AN:

35334

Ashkenazi Jewish (ASJ)

AF:

0.541

AC:

13413

AN:

24810

East Asian (EAS)

AF:

0.305

AC:

10861

AN:

35604

South Asian (SAS)

AF:

0.500

AC:

39197

AN:

78376

European-Finnish (FIN)

AF:

0.610

AC:

29506

AN:

48404

Middle Eastern (MID)

AF:

0.455

AC:

2570

AN:

5654

European-Non Finnish (NFE)

AF:

0.586

AC:

628547

AN:

1073416

Other (OTH)

AF:

0.537

AC:

30949

AN:

57636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

14833

29666

44500

59333

74166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17488

34976

52464

69952

87440

<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:

0.531

AC:

80802

AN:

152078

Hom.:

21740

Cov.:

AF XY:

0.529

AC XY:

39348

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.483

AC:

20030

AN:

41506

American (AMR)

AF:

0.457

AC:

6990

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1866

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1726

AN:

5158

South Asian (SAS)

AF:

0.478

AC:

2306

AN:

4826

European-Finnish (FIN)

AF:

0.613

AC:

6482

AN:

10582

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.583

AC:

39612

AN:

67930

Other (OTH)

AF:

0.512

AC:

1084

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

1918

3835

5753

7670

9588

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

700

1400

2100

2800

3500

<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:

0.557

Hom.:

59745

Bravo

AF:

0.516

Asia WGS

AF:

0.416

AC:

1449

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 14, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acrocallosal syndrome

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hydrolethalus syndrome 2

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Multiple epiphyseal dysplasia, Al-Gazali type

Benign:1

Aug 19, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

2.1

(source)

DANN

Benign

0.45

PhyloP100

-0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over