VCV000129415.41 - ClinVar

NM_198525.3(KIF7):c.3345C>G (p.His1115Gln)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(11)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_198525.3(KIF7):c.3345C>G (p.His1115Gln)

Variation ID: 129415 Accession: VCV000129415.41

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q26.1 15: 89629547 (GRCh38) [ NCBI UCSC ] 15: 90172778 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 6, 2014	Oct 20, 2024	Aug 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_198525.3:c.3345C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_940927.2:p.His1115Gln	missense
NC_000015.10:g.89629547G>C
NC_000015.9:g.90172778G>C
NG_030338.1:g.30905C>G
	Q2M1P5:p.His1115Gln

... more HGVS ... less HGVS

Protein change

H1115Q

Other names

p.H1115Q:CAC>CAG
NM_198525.2(KIF7):c.3345C>G(p.His1115Gln)

Canonical SPDI

NC_000015.10:89629546:G:C

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00579 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 0.00579

Trans-Omics for Precision Medicine (TOPMed) 0.01286

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01746

1000 Genomes Project 30x 0.00547

Links

ClinGen: CA020358 UniProtKB: Q2M1P5#VAR_066457 dbSNP: rs142032413 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
KIF7		-	-	GRCh38 GRCh37	1281	1553
LOC126862216	-	-	-	GRCh38	-	150

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign (4)	criteria provided, multiple submitters, no conflicts	Jan 6, 2015	RCV000117422.18
Acrocallosal syndrome	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2024	RCV000363675.16
Hydrolethalus syndrome 2	Benign (1)	criteria provided, single submitter	May 31, 2018	RCV000677323.3
Scoliosis, isolated, susceptibility to, 1	Uncertain significance (1)	no assertion criteria provided	Feb 1, 2020	RCV001290030.4
not provided	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Aug 1, 2024	RCV002262708.17
Acrocallosal syndrome Hydrolethalus syndrome 2 Multiple epiphyseal dysplasia, Al-Gazali type	Likely benign (1)	criteria provided, single submitter	Oct 5, 2021	RCV002490798.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Apr 15, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000170020.10 First in ClinVar: Jun 23, 2014 Last updated: Oct 02, 2016	Comment: 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 … (more) 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. (less)
Benign (May 31, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: curation	Hydrolethalus syndrome 2 Affected status: unknown Allele origin: unknown	SIB Swiss Institute of Bioinformatics Accession: SCV000803539.1 First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018	Comment: This variant is interpreted as a Benign, for Hydrolethalus syndrome 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PS3-Moderate => PS3 downgraded … (more) This variant is interpreted as a Benign, for Hydrolethalus syndrome 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PS3-Moderate => PS3 downgraded in strength to Moderate. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Acrocallosal syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000394320.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (1) PubMed: 21552264 Comment: 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, … (more) 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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Oct 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Acrocallosal syndrome Multiple epiphyseal dysplasia, Al-Gazali type Hydrolethalus syndrome 2 Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002796726.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Jan 31, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Acrocallosal syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000636832.6 First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000316991.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jan 06, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000226707.5 First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KIF7 http://exac.broadinstitute.org/g… http://exac.broadinstitute.org/gene/ENSG00000166813 http://www.ncbi.nlm.nih.gov/vari… http://www.ncbi.nlm.nih.gov/variation/tools/1000genomes/?chr=15&from=90172778&to=90172778 Number of individuals with the variant: 2 Sex: mixed
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005213955.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (Aug 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002545311.16 First in ClinVar: Jul 09, 2022 Last updated: Oct 20, 2024	Comment: KIF7: BS1, BS2 Number of individuals with the variant: 46
Likely benign (-)	no assertion criteria provided Method: clinical testing	AllHighlyPenetrant (Autosomal recessive inheritance) Affected status: unknown Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV000151623.2 First in ClinVar: May 17, 2014 Last updated: Jul 06, 2014	Comment: 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 … (more) 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. (less)
Uncertain significance (Feb 01, 2020)	no assertion criteria provided Method: case-control	Scoliosis, isolated, susceptibility to, 1 Affected status: no, yes Allele origin: germline	Miller Scoliosis Laboratory, University of Colorado Anschutz Medical Campus Accession: SCV001426138.1 First in ClinVar: Jan 30, 2021 Last updated: Jan 30, 2021 Comment: All individuals within a single family. All individuals possessing variant were affected, except for one unaffected obligate carrier.	Comment: Several affected individuals within a multigenerational family possess the variant in question. Mutations in this gene were also found to cause scoliosis in a zebrafish … (more) Several affected individuals within a multigenerational family possess the variant in question. Mutations in this gene were also found to cause scoliosis in a zebrafish model. (less) Observation 1: Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 2: Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 3: Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 4: Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 5: Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 6: Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20 Observation 7: Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: Caucasian Geographic origin: United States Testing laboratory: University of Colorado Anschutz Medical Campus Date variant was reported to submitter: 2019-05-20
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Comment:

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.

Comment:

This variant is interpreted as a Benign, for Hydrolethalus syndrome 2, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PS3-Moderate => PS3 downgraded in strength to Moderate. BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.

Comment:

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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
KIF7 mutations cause fetal hydrolethalus and acrocallosal syndromes.	Putoux A	Nature genetics	2011	PMID: 21552264
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KIF7	-	-	-	-

Text-mined citations for rs142032413 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Oct 20, 2024

ClinVar Genomic variation as it relates to human health

NM_198525.3(KIF7):c.3345C>G (p.His1115Gln)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs142032413 ...