15-89633201-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_198525.3(KIF7):c.2658A>C(p.Ala886Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.892 in 1,603,078 control chromosomes in the GnomAD database, including 641,161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.85 ( 55566 hom., cov: 32)

Exomes 𝑓: 0.90 ( 585595 hom. )

Consequence

KIF7
NM_198525.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: -1.05

Publications

24 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 15-89633201-T-G is Benign according to our data. Variant chr15-89633201-T-G is described in ClinVar as Benign. ClinVar VariationId is 129413.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.2658A>C	p.Ala886Ala	synonymous_variant	Exon 13 of 19	ENST00000394412.8	NP_940927.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
KIF7	ENST00000394412.8 link	c.2658A>C	p.Ala886Ala	synonymous_variant	Exon 13 of 19	5	NM_198525.3	ENSP00000377934.3
KIF7	ENST00000696512.1 link	c.2781A>C	p.Ala927Ala	synonymous_variant	Exon 13 of 19			ENSP00000512678.1
KIF7	ENST00000677187.1 link	n.332A>C		non_coding_transcript_exon_variant	Exon 1 of 7

Frequencies

GnomAD3 genomes

AF:

0.852

AC:

129491

AN:

152040

Hom.:

55528

Cov.:

show subpopulations

Gnomad AFR

AF:

0.782

Gnomad AMI

AF:

0.949

Gnomad AMR

AF:

0.771

Gnomad ASJ

AF:

0.836

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.858

Gnomad NFE

AF:

0.918

Gnomad OTH

AF:

0.856

GnomAD2 exomes

AF:

0.849

AC:

200975

AN:

236596

AF XY:

0.858

show subpopulations

Gnomad AFR exome

AF:

0.779

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.843

Gnomad EAS exome

AF:

0.701

Gnomad FIN exome

AF:

0.882

Gnomad NFE exome

AF:

0.916

Gnomad OTH exome

AF:

0.868

GnomAD4 exome

AF:

0.896

AC:

1300671

AN:

1450920

Hom.:

585595

Cov.:

AF XY:

0.897

AC XY:

647197

AN XY:

721534

show subpopulations

African (AFR)

AF:

0.776

AC:

25875

AN:

33364

American (AMR)

AF:

0.723

AC:

31731

AN:

43918

Ashkenazi Jewish (ASJ)

AF:

0.848

AC:

22037

AN:

25982

East Asian (EAS)

AF:

0.669

AC:

26427

AN:

39526

South Asian (SAS)

AF:

0.873

AC:

74323

AN:

85146

European-Finnish (FIN)

AF:

0.886

AC:

41984

AN:

47404

Middle Eastern (MID)

AF:

0.864

AC:

4815

AN:

5576

European-Non Finnish (NFE)

AF:

0.919

AC:

1020401

AN:

1109882

Other (OTH)

AF:

0.883

AC:

53078

AN:

60122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

7288

14577

21865

29154

36442

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21418

42836

64254

85672

107090

<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:

0.852

AC:

129582

AN:

152158

Hom.:

55566

Cov.:

AF XY:

0.848

AC XY:

63081

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.782

AC:

32444

AN:

41498

American (AMR)

AF:

0.771

AC:

11784

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.836

AC:

2901

AN:

3472

East Asian (EAS)

AF:

0.701

AC:

3605

AN:

5142

South Asian (SAS)

AF:

0.848

AC:

4095

AN:

4828

European-Finnish (FIN)

AF:

0.888

AC:

9429

AN:

10618

Middle Eastern (MID)

AF:

0.857

AC:

252

AN:

294

European-Non Finnish (NFE)

AF:

0.918

AC:

62409

AN:

68006

Other (OTH)

AF:

0.852

AC:

1799

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

954

1908

2862

3816

4770

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

890

1780

2670

3560

4450

<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:

0.883

Hom.:

31875

Bravo

AF:

0.836

Asia WGS

AF:

0.772

AC:

2687

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Dec 22, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.92

CADD

Benign

0.25

(source)

DANN

Benign

0.42

PhyloP100

-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