VCV000088681.1 - ClinVar

NC_000008.11:g.100151617_100163589del

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.

(2)

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.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000008.11:g.100151617_100163589del

Variation ID: 88681 Accession: VCV000088681.1

Type and length

Deletion, 11,973 bp

Location

Cytogenetic: 8q22 8: 100151617-100163589 (GRCh38) [ NCBI UCSC ] 8: 101163845-101175817 (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 14, 2013	Sep 29, 2015	Sep 3, 2015

HGVS

Nucleotide	Protein	Molecular consequence
NC_000008.11:g.100151617_100163589del
NC_000008.10:g.101163845_101175817del

Protein change

Other names

11.97-KB DEL

Canonical SPDI

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.

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

Links

OMIM: 603395.0002 VarSome

Comment on variant

11.97-KB deletion from intron 2 of POLR2K to intron 2 of SPAG1.

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.
LOC130000829	-	-	-	GRCh38	-	17
LOC130000830	-	-	-	GRCh38	-	17
POLR2K		-	-	GRCh38 GRCh37	3	47
SPAG1		-	-	GRCh38 GRCh37	385	501

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.
Primary ciliary dyskinesia 28	Pathogenic (1)	no assertion criteria provided	Oct 3, 2013	RCV000074364.3
Kartagener syndrome	Pathogenic (1)	no assertion criteria provided	Sep 3, 2015	RCV000190931.1

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.
Pathogenic (Oct 03, 2013)	no assertion criteria provided Method: literature only	CILIARY DYSKINESIA, PRIMARY, 28, WITH OR WITHOUT SITUS INVERSUS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000105971.2 First in ClinVar: Nov 14, 2013 Last updated: Nov 14, 2013	Publications: PubMed (1) PubMed: 24055112 Comment on evidence: In affected members of 4 unrelated families with CILD28 with or without situs inversus (615505), Knowles et al. (2013) identified compound heterozygous mutations in the … (more) In affected members of 4 unrelated families with CILD28 with or without situs inversus (615505), Knowles et al. (2013) identified compound heterozygous mutations in the SPAG1 gene. One of the alleles shared by all 4 families was a large 11.97-kb deletion (c.61+201_POLR2K:c.140+1169_SPAG1del) comprising multiple introns, exons, and untranslated regions from the 3-prime region of the POLR2K (606033) gene to the 5-prime region of the SPAG1 gene. The deletion included the translation start codon of SPAG1 and was predicted to abrogate SPAG1 translation. Haplotype analysis indicated a founder effect for this deletion all families. The other mutant allele in 1 family was M1? (603395.0001) and in 2 families was Q672X (603395.0004). Heterozygous disruption of the POLR2K was thought not to contribute to the phenotype. (less)
Pathogenic (Sep 03, 2015)	no assertion criteria provided Method: literature only	Kartagener syndrome Affected status: yes Allele origin: germline	GeneReviews Accession: SCV000245817.1 First in ClinVar: Sep 29, 2015 Last updated: Sep 29, 2015	Publications: PubMed (1) PubMed: 24055112 Other databases http://www.ncbi.nlm.nih.gov/book… http://www.ncbi.nlm.nih.gov/books/NBK1122/

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Primary Ciliary Dyskinesia.	Adam MP	-	2019	PMID: 20301301
Mutations in SPAG1 cause primary ciliary dyskinesia associated with defective outer and inner dynein arms.	Knowles MR	American journal of human genetics	2013	PMID: 24055112

Text-mined citations for this variant ...

Record last updated Oct 15, 2023

ClinVar Genomic variation as it relates to human health

NC_000008.11:g.100151617_100163589del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...