VCV000029930.2 - ClinVar

SMC1A, 8.152-KB 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

SMC1A, 8.152-KB DEL

Variation ID: 29930 Accession: VCV000029930.2

Type and length

Deletion, -

Location

Cytogenetic: Xp11.22-p11.21 -

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	Apr 18, 2020	Apr 18, 2020	Jan 1, 2012

HGVS

Protein change

Other names

8.152-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: 300040.0006

Comment on variant

8152-nt deletion from exon 13 to intron 16 of gene SMC1A.

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.
SMC1A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	918	1086

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.
Congenital muscular hypertrophy-cerebral syndrome	Pathogenic (1)	no assertion criteria provided	Jan 1, 2012	RCV000022821.18

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, 2012)	no assertion criteria provided Method: literature only	CORNELIA DE LANGE SYNDROME 2 Affected status: not provided Allele origin: germline	OMIM Accession: SCV000044110.3 First in ClinVar: Apr 04, 2013 Last updated: Apr 18, 2020	Publications: PubMed (1) PubMed: 22106055 Comment on evidence: In a girl with a severe form of Cornelia de Lange syndrome-2 (CDLS2; 300590), Hoppman-Chaney et al. (2012) identified a de novo heterozygous 8.152-kb deletion … (more) In a girl with a severe form of Cornelia de Lange syndrome-2 (CDLS2; 300590), Hoppman-Chaney et al. (2012) identified a de novo heterozygous 8.152-kb deletion encompassing exon 13 to intron 16 of the SMC1A gene, resulting in an in-frame deletion of 126 amino acids and insertion of 3 novel amino acids. The mutant mRNA was expressed, and Hoppman-Chaney et al. (2012) concluded that the mutant protein lacking the coiled-coil domain would act in a dominant-negative manner. The patient had dysmorphic facial features, microcephaly, poor growth, profound psychomotor retardation, holoprosencephaly, right hemihypertrophy, and mild distal limb anomalies. The patient was also mosaic for Turner syndrom, 45,X(7)/46,XX(23), which may have accounted for some additional features. (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
In-frame multi-exon deletion of SMC1A in a severely affected female with Cornelia de Lange Syndrome.	Hoppman-Chaney N	American journal of medical genetics. Part A	2012	PMID: 22106055

Text-mined citations for this variant ...

Record last updated Nov 19, 2022

ClinVar Genomic variation as it relates to human health

SMC1A, 8.152-KB DEL

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...