VCV002685692.1 - ClinVar

GRCh37/hg19 Xp22.31(chrX:6591135-9498909)x1

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 Xp22.31(chrX:6591135-9498909)x1

Variation ID: 2685692 Accession: VCV002685692.1

Type and length

copy number loss, -

Location

Cytogenetic: Xp22.31 X: 6591135-9498909 (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	Jan 26, 2024	Jan 26, 2024	Jan 5, 2023

HGVS

Protein change

Other names

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

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.
ANOS1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	285	516
STS		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	128	512
FAM9A		-	-	GRCh38 GRCh37	20	219
FAM9B		-	-	GRCh38 GRCh37	18	202
PNPLA4		-	-	GRCh38 GRCh37	11	400
PUDP		-	-	GRCh38 GRCh37	22	406
TBL1X		-	-	GRCh38 GRCh37	72	258
VCX		-	-	GRCh38 GRCh37	7	367
VCX2		-	-	GRCh38 GRCh37	3	294
VCX3B		-	-	GRCh38 GRCh37	85	305

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 provided	Pathogenic (1)	criteria provided, single submitter	Jan 5, 2023	RCV003483409.1

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 (Jan 05, 2023)	criteria provided, single submitter (ACMG/ClinGen CNV Guidelines, 2019) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV004230324.1 First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024	Comment: This copy number loss contains several protein-coding genes and overlaps the Xp22.31 microdeletion region, including genes STS (OMIM 300747) and ANOS1 (OMIM 300836). Together, loss … (more) This copy number loss contains several protein-coding genes and overlaps the Xp22.31 microdeletion region, including genes STS (OMIM 300747) and ANOS1 (OMIM 300836). Together, loss of both of these genes is considered a contiguous gene deletion syndrome (Berges-Raso 2017, Ma 2020, Nagai 2017, Rehm 2015 (ISCA-37417)). Furthermore, missense and loss-of-function variants of TBL1X have been associated with variable presentation of hearing loss and/or hypothyroidism (Bassi 1999, Garcia 2018, Heinen 2016, Sugisawa 2019). There are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, this copy number variant (CNV) is classified as pathogenic. References: Bassi et al., Am J Hum Genet. 1999 Jun;64(6):1604-16. PMID: 10330347 Berges-Raso et al., Endocrinol Diabetes Metab Case Rep. 2017 Sep 28;2017:EDM170083. PMID: 30352392 Garcia et al., J Endocr Soc. 2018 Nov 23;3(1):119-128. PMID: 30591955 Heinen et al., J Clin Endocrinol Metab. 2016 Dec;101(12):4564-4573. PMID: 27603907 Ma et al., Front Genet. 2020 Jun 24;11:596. PMID: 32670353 Nagai et al., Cytogenet Genome Res. 2017;151(1):1-4. PMID: 28253503 Rehm et al., N Engl J Med. 2015 Jun 4;372(23):2235-42. PMID: 26014595 (ISCA-37417) Sugisawa et al., J Clin Endocrinol Metab. 2019 Dec 1;104(12):6229-6237. PMID: 31504637 (less)

Comment:

This copy number loss contains several protein-coding genes and overlaps the Xp22.31 microdeletion region, including genes STS (OMIM 300747) and ANOS1 (OMIM 300836). Together, loss of both of these genes is considered a contiguous gene deletion syndrome (Berges-Raso 2017, Ma 2020, Nagai 2017, Rehm 2015 (ISCA-37417)). Furthermore, missense and loss-of-function variants of TBL1X have been associated with variable presentation of hearing loss and/or hypothyroidism (Bassi 1999, Garcia 2018, Heinen 2016, Sugisawa 2019). There are no similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, this copy number variant (CNV) is classified as pathogenic. References: Bassi et al., Am J Hum Genet. 1999 Jun;64(6):1604-16. PMID: 10330347 Berges-Raso et al., Endocrinol Diabetes Metab Case Rep. 2017 Sep 28;2017:EDM170083. PMID: 30352392 Garcia et al., J Endocr Soc. 2018 Nov 23;3(1):119-128. PMID: 30591955 Heinen et al., J Clin Endocrinol Metab. 2016 Dec;101(12):4564-4573. PMID: 27603907 Ma et al., Front Genet. 2020 Jun 24;11:596. PMID: 32670353 Nagai et al., Cytogenet Genome Res. 2017;151(1):1-4. PMID: 28253503 Rehm et al., N Engl J Med. 2015 Jun 4;372(23):2235-42. PMID: 26014595 (ISCA-37417) Sugisawa et al., J Clin Endocrinol Metab. 2019 Dec 1;104(12):6229-6237. PMID: 31504637

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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Feb 04, 2024

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 Xp22.31(chrX:6591135-9498909)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...