VCV000375673.1 - ClinVar

NM_152524.5:c.1453_1454delGA,NM_012130.3:c.254T>A

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.

(1)

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

This haplotype includes the following variants

NM_152524.5:c.1453_1454delGA,NM_012130.3:c.254T>A

Other names: -
Functional consequence: -
Links: -

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.
CLDN14		-	-	GRCh38 GRCh37	-	225
CLDN14-AS1	-	-	-	GRCh38	-	192
SGO2		-	-	GRCh38 GRCh37	14	48

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.
Perrault syndrome	Pathogenic (1)	no assertion criteria provided	Aug 30, 2016	RCV000417144.2

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.
Pathogenic (Aug 30, 2016)	no assertion criteria provided Method: research	Perrault Syndrome Affected status: yes Allele origin: germline	Laboratory of Molecular Genetics, National Institutes of Health Accession: SCV000494729.1 First in ClinVar: Feb 19, 2017 Last updated: Feb 19, 2017	Comment: A proband was diagnosed with Perrault syndrome. She does not have a pathogenic variant in any of the reported Pearrult syndrome genes. The proband is … (more) A proband was diagnosed with Perrault syndrome. She does not have a pathogenic variant in any of the reported Pearrult syndrome genes. The proband is deaf and has ovarian dysfunction. Surprisingly, her deafness is due to a homozygous reported variant of CLDN14, while her POI is due to a homozygous truncating mutation of SGO2. This is the first description in human of a pathogenic variant of SGO2. However, in mouse homozygous mutations of Sgol2 encoding shugushin 2 are known to be necessary for meiosis. Loss of function of Sgol2 cause infertility in both males and females. (less) Clinical Features: Deafness (present) , Primary ovarian insufficiency (present)

Comment:

A proband was diagnosed with Perrault syndrome. She does not have a pathogenic variant in any of the reported Pearrult syndrome genes. The proband is deaf and has ovarian dysfunction. Surprisingly, her deafness is due to a homozygous reported variant of CLDN14, while her POI is due to a homozygous truncating mutation of SGO2. This is the first description in human of a pathogenic variant of SGO2. However, in mouse homozygous mutations of Sgol2 encoding shugushin 2 are known to be necessary for meiosis. Loss of function of Sgol2 cause infertility in both males and females.

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
Global genetic insight contributed by consanguineous Pakistani families segregating hearing loss.	Richard EM	Human mutation	2019	PMID: 30303587
Novel CLDN14 mutations in Pakistani families with autosomal recessive non-syndromic hearing loss.	Lee K	American journal of medical genetics. Part A	2012	PMID: 22246673
Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions in vitro.	Wattenhofer M	Human mutation	2005	PMID: 15880785
Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29.	Wilcox ER	Cell	2001	PMID: 11163249

Text-mined citations for this variant ...

Record last updated Jul 29, 2024

ClinVar Genomic variation as it relates to human health

NM_152524.5:c.1453_1454delGA,NM_012130.3:c.254T>A

Variant Details

NM_152524.5:c.1453_1454delGA,NM_012130.3:c.254T>A

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...