VCV000010706.2 - ClinVar

NC_000023.11:g.(57537466_63428182)_(65235775_65512709)del

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

Identifiers

NC_000023.11:g.(57537466_63428182)_(65235775_65512709)del

Variation ID: 10706 Accession: VCV000010706.2

Type and length

Deletion, 7,975,244 bp

Location

Cytogenetic: Xp11.21-q12 X: 57537466-65512709 (GRCh38) [ 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	Mar 14, 2021	Mar 14, 2021	Jan 1, 2010

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.11:g.(57537466_63428182)_(65235775_65512709)del

Protein change

Other names

AMER1, DEL
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: 300647.0003 VarSome

Comment on variant

Deletion of the entire AMER1 gene plus flanking sequences.

NCBI staff generated an HGVS expression for the 300647.0003 based on rough estimates from the diagram in Figure 1 of the paper by Perdu et al., 2010 (PubMed 20209645). The diagram and probe locations were based on NC_000023.9 (NCBI36) and mapped to GRCh38.

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.
ARHGEF9		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	445	578
ZC4H2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	174	305
AMER1		-	-	GRCh38 GRCh37	453	588
ARHGEF9-IT1	-	-	-	GRCh38	-	66
ASB12		-	-	GRCh38 GRCh37	23	156
LAS1L		-	-	GRCh38 GRCh37	178	303
LINC01278	-	-	-	GRCh38	-	66
LOC113875034	-	-	-	GRCh38	-	64
LOC121627974	-	-	-	GRCh38	-	67
LOC121853058	-	-	-	GRCh38	-	74

There are 28 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh38).

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.
Osteopathia striata with cranial sclerosis	Pathogenic (1)	no assertion criteria provided	Jan 1, 2010	RCV000011452.8

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 01, 2010)	no assertion criteria provided Method: literature only	OSTEOPATHIA STRIATA WITH CRANIAL SCLEROSIS Affected status: not provided Allele origin: germline	OMIM Accession: SCV000031684.4 First in ClinVar: Apr 04, 2013 Last updated: Mar 14, 2021	Publications: PubMed (3) PubMed: 19079258‚ 9383023‚ 20209645 Comment on evidence: In 2 unrelated females with osteopathia striata with cranial sclerosis (OSCS; 300373), Jenkins et al. (2009) identified deletion of the entire AMER1 gene with undetectable … (more) In 2 unrelated females with osteopathia striata with cranial sclerosis (OSCS; 300373), Jenkins et al. (2009) identified deletion of the entire AMER1 gene with undetectable protein and normal X-inactivation ratio. In affected female members of a large family with OSCS originally reported by Savarirayan et al. (1997), Perdu et al. (2010) identified a deletion of the WTX gene. The family showed a highly variable phenotype. The proband had multiple congenital abnormalities, whereas her mother, maternal grandmother, and maternal great-grandmother were less severely affected. The mother of the proband had a subsequent pregnancy; the fetus was found to have alobar holoprosencephaly, cleft lip and palate, and partial absence of the nose. The pregnancy was terminated, and radiographs showed abnormal sclerosis of the maxilla, mandible, and orbital roofs. (less)

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
Osteopathia striata with cranial sclerosis owing to WTX gene defect.	Perdu B	Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research	2010	PMID: 20209645
Germline mutations in WTX cause a sclerosing skeletal dysplasia but do not predispose to tumorigenesis.	Jenkins ZA	Nature genetics	2009	PMID: 19079258
Osteopathia striata with cranial sclerosis: highly variable phenotypic expression within a family.	Savarirayan R	Clinical genetics	1997	PMID: 9383023

Text-mined citations for this variant ...

Record last updated Oct 15, 2023

ClinVar Genomic variation as it relates to human health

NC_000023.11:g.(57537466_63428182)_(65235775_65512709)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...