rs149814240

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_198525.3(KIF7):c.1885G>A(p.Glu629Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,613,772 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 45 hom. )

Consequence

KIF7
NM_198525.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 0.0940

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 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 (MetaRNN=0.0034671128).

BP6

Variant 15-89645930-C-T is Benign according to our data. Variant chr15-89645930-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 263139.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-89645930-C-T is described in Lovd as [Benign]. Variant chr15-89645930-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00503 (766/152308) while in subpopulation NFE AF = 0.00813 (553/68008). AF 95% confidence interval is 0.00757. There are 7 homozygotes in GnomAd4. There are 390 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIF7	NM_198525.3 link	c.1885G>A	p.Glu629Lys	missense_variant	Exon 8 of 19	ENST00000394412.8	NP_940927.2	Q2M1P5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF7	ENST00000394412.8 link	c.1885G>A	p.Glu629Lys	missense_variant	Exon 8 of 19	5	NM_198525.3	ENSP00000377934.3		Q2M1P5
KIF7	ENST00000696512.1 link	c.2008G>A	p.Glu670Lys	missense_variant	Exon 8 of 19			ENSP00000512678.1		A0A8Q3SIQ8

Frequencies

GnomAD3 genomes

AF:

0.00503

AC:

766

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00813

Gnomad OTH

AF:

0.00143

GnomAD2 exomes

AF:

0.00531

AC:

1334

AN:

251068

AF XY:

0.00510

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00457

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0164

Gnomad NFE exome

AF:

0.00766

Gnomad OTH exome

AF:

0.00603

GnomAD4 exome

AF:

0.00427

AC:

6244

AN:

1461464

Hom.:

Cov.:

AF XY:

0.00436

AC XY:

3170

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.000299

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.000626

AC:

AN:

44716

Gnomad4 ASJ exome

AF:

0.00643

AC:

168

AN:

26134

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39700

Gnomad4 SAS exome

AF:

0.0000116

AC:

AN:

86256

Gnomad4 FIN exome

AF:

0.0162

AC:

858

AN:

53064

Gnomad4 NFE exome

AF:

0.00447

AC:

4973

AN:

1111962

Gnomad4 Remaining exome

AF:

0.00339

AC:

205

AN:

60388

Heterozygous variant carriers

386

772

1159

1545

1931

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<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:

0.00503

AC:

766

AN:

152308

Hom.:

Cov.:

AF XY:

0.00524

AC XY:

390

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000361

AC:

0.000360855

AN:

0.000360855

Gnomad4 AMR

AF:

0.000457

AC:

0.000457337

AN:

0.000457337

Gnomad4 ASJ

AF:

0.00432

AC:

0.00432277

AN:

0.00432277

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.0163

AC:

0.0162778

AN:

0.0162778

Gnomad4 NFE

AF:

0.00813

AC:

0.0081314

AN:

0.0081314

Gnomad4 OTH

AF:

0.00142

AC:

0.00141911

AN:

0.00141911

Heterozygous variant carriers

120

160

200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

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:

0.00626

Hom.:

Bravo

AF:

0.00264

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00592

AC:

719

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00474

EpiControl

AF:

0.00362

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Aug 23, 2022

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Likely 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

- -

Aug 04, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 16, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:5

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIF7: BP4, BS2 -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Acrocallosal syndrome

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Acrocallosal syndrome;C1846722:Multiple epiphyseal dysplasia, Al-Gazali type;C3279899:Hydrolethalus syndrome 2

Benign:1

Oct 22, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.32

CADD

Benign

9.0

DANN

Benign

0.57

DEOGEN2

Benign

0.14

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.51

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.44

PROVEAN

Benign

-0.78

REVEL

Benign

0.12

Sift

Benign

0.61

Sift4G

Benign

0.81

Polyphen

0.018

Vest4

0.21

MVP

0.38

MPC

0.019

ClinPred

0.018

GERP RS

1.7

Varity_R

0.045

gMVP

0.40

Mutation Taster

=90/10

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