15-89646817-A-G

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.1788+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,612,020 control chromosomes in the GnomAD database, including 294,590 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 26907 hom., cov: 31)

Exomes 𝑓: 0.60 ( 267683 hom. )

Consequence

KIF7
NM_198525.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -2.76

Publications

17 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=-0.79).

BP6

Variant 15-89646817-A-G is Benign according to our data. Variant chr15-89646817-A-G is described in ClinVar as [Benign]. Clinvar id is 263138.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.1788+13T>C		intron_variant	Intron 7 of 18	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8 link	c.1788+13T>C		intron_variant	Intron 7 of 18	5	NM_198525.3	ENSP00000377934.3		Q2M1P5
KIF7	ENST00000696512.1 link	c.1911+13T>C		intron_variant	Intron 7 of 18			ENSP00000512678.1		A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89796

AN:

151668

Hom.:

26878

Cov.:

show subpopulations

Gnomad AFR

AF:

0.617

Gnomad AMI

AF:

0.632

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.551

Gnomad EAS

AF:

0.366

Gnomad SAS

AF:

0.480

Gnomad FIN

AF:

0.629

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.619

Gnomad OTH

AF:

0.564

GnomAD2 exomes

AF:

0.560

AC:

140214

AN:

250600

AF XY:

0.562

show subpopulations

Gnomad AFR exome

AF:

0.623

Gnomad AMR exome

AF:

0.439

Gnomad ASJ exome

AF:

0.562

Gnomad EAS exome

AF:

0.357

Gnomad FIN exome

AF:

0.625

Gnomad NFE exome

AF:

0.623

Gnomad OTH exome

AF:

0.571

GnomAD4 exome

AF:

0.602

AC:

878687

AN:

1460234

Hom.:

267683

Cov.:

AF XY:

0.599

AC XY:

435368

AN XY:

726522

show subpopulations

African (AFR)

AF:

0.619

AC:

20701

AN:

33428

American (AMR)

AF:

0.447

AC:

19967

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

14709

AN:

26130

East Asian (EAS)

AF:

0.340

AC:

13509

AN:

39690

South Asian (SAS)

AF:

0.502

AC:

43265

AN:

86220

European-Finnish (FIN)

AF:

0.627

AC:

33489

AN:

53388

Middle Eastern (MID)

AF:

0.524

AC:

2766

AN:

5278

European-Non Finnish (NFE)

AF:

0.625

AC:

694961

AN:

1111092

Other (OTH)

AF:

0.586

AC:

35320

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

17529

35059

52588

70118

87647

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.592

AC:

89870

AN:

151786

Hom.:

26907

Cov.:

AF XY:

0.589

AC XY:

43705

AN XY:

74154

show subpopulations

African (AFR)

AF:

0.616

AC:

25511

AN:

41386

American (AMR)

AF:

0.505

AC:

7707

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.551

AC:

1911

AN:

3468

East Asian (EAS)

AF:

0.368

AC:

1878

AN:

5110

South Asian (SAS)

AF:

0.479

AC:

2302

AN:

4802

European-Finnish (FIN)

AF:

0.629

AC:

6638

AN:

10548

Middle Eastern (MID)

AF:

0.554

AC:

163

AN:

294

European-Non Finnish (NFE)

AF:

0.619

AC:

42001

AN:

67900

Other (OTH)

AF:

0.561

AC:

1183

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1899

3797

5696

7594

9493

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.600

Hom.:

43758

Bravo

AF:

0.584

Asia WGS

AF:

0.437

AC:

1521

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

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

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

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 12, 2016

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

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

-0.79

CADD

Benign

0.017

(source)

DANN

Benign

0.72

PhyloP100

-2.8

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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15-89646817-A-G

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