VCV000194572.30 - ClinVar

NM_198525.3(KIF7):c.2981A>G (p.Gln994Arg)

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.

(8)

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.2981A>G (p.Gln994Arg)

Variation ID: 194572 Accession: VCV000194572.30

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 15q26.1 15: 89631625 (GRCh38) [ NCBI UCSC ] 15: 90174856 (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	Nov 9, 2015	Oct 20, 2024	May 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_198525.3:c.2981A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_940927.2:p.Gln994Arg	missense
NC_000015.10:g.89631625T>C
NC_000015.9:g.90174856T>C
NG_030338.1:g.28827A>G
	Q2M1P5:p.Gln994Arg

... more HGVS ... less HGVS

Protein change

Q994R

Other names

Canonical SPDI

NC_000015.10:89631624:T: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.

0.00220 (C)

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

1000 Genomes Project 0.00220

Trans-Omics for Precision Medicine (TOPMed) 0.00226

1000 Genomes Project 30x 0.00250

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00116

Exome Aggregation Consortium (ExAC) 0.00153

The Genome Aggregation Database (gnomAD), exomes 0.00164

The Genome Aggregation Database (gnomAD) 0.00203

Links

ClinGen: CA020312 UniProtKB: Q2M1P5#VAR_066455 dbSNP: rs138410949 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

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.
Acrocallosal syndrome	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Jan 26, 2024	RCV000201541.24
not provided	Likely benign (4)	criteria provided, multiple submitters, no conflicts	May 1, 2024	RCV000513744.31
Intellectual disability	no classifications from unflagged records (1)	no classifications from unflagged records	Dec 4, 2023	RCV001252541.11

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.
Likely benign (Jan 26, 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: SCV001020715.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 28, 2024
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: SCV001280350.1 First in ClinVar: May 31, 2020 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 rule this variant out of causing disease. Therefore, this variant is classified as benign. (less)
Likely benign (Mar 11, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000329378.7 First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023	Comment: In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23891399, 26092869, 26648833, … (more) In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23891399, 26092869, 26648833, 21552264, 31322791) (less)
Likely benign (May 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: SCV004130861.10 First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024	Comment: KIF7: BP4, BS2 Number of individuals with the variant: 3
Pathogenic (Feb 23, 2015)	Flagged submission flagged submission (Bachmann-Gagescu et al. (J Med Genet. 2015)) Method: research Reason: Outlier claim with insufficient supporting evidence Source: ClinGen	Acrocallosal syndrome Affected status: yes Allele origin: unknown	UW Hindbrain Malformation Research Program, University of Washington Additional submitter: University of Washington Center for Mendelian Genomics, University of Washington Accession: SCV000256440.1 First in ClinVar: Nov 09, 2015 Last updated: Nov 09, 2015	Publications: PubMed (1) PubMed: 26092869
Uncertain significance (Mar 28, 2017)	Flagged submission flagged submission (ACMG Guidelines, 2015) Method: clinical testing Reason: Older claim that does not account for recent evidence Source: ClinGen	not provided Affected status: not provided Allele origin: germline	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics Accession: SCV000610688.1 First in ClinVar: Nov 05, 2017 Last updated: Nov 05, 2017
Uncertain significance (Nov 14, 2014)	Flagged submission flagged submission (EGL Classification Definitions 2015) Method: clinical testing Reason: Older claim that does not account for recent evidence Source: ClinGen	not provided Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000226370.5 First in ClinVar: Jun 29, 2015 Last updated: Dec 15, 2018	Publications: PubMed (1) PubMed: 21552264 Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=KIF7 Number of individuals with the variant: 2 Sex: mixed
Uncertain significance (Jan 01, 2019)	Flagged submission flagged submission Method: clinical testing Reason: Claim with insufficient supporting evidence Source: ClinGen	Intellectual disability Affected status: yes Allele origin: unknown	Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille Accession: SCV001428298.1 First in ClinVar: Aug 15, 2020 Last updated: Aug 15, 2020	Publications: PubMed (1) PubMed: 25741868
Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more

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 rule this variant out of causing disease. Therefore, this variant is classified as 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
Joubert syndrome: a model for untangling recessive disorders with extreme genetic heterogeneity.	Bachmann-Gagescu R	Journal of medical genetics	2015	PMID: 26092869
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.	Richards S	Genetics in medicine : official journal of the American College of Medical Genetics	2015	PMID: 25741868
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 rs138410949 ...

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 Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_198525.3(KIF7):c.2981A>G (p.Gln994Arg)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs138410949 ...