VCV002425562.4 - ClinVar

NC_000023.10:g.(?_53222149)_(55057617_?)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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NC_000023.10:g.(?_53222149)_(55057617_?)del

Variation ID: 2425562 Accession: VCV002425562.4

Type and length

Deletion, 1,835,469 bp

Location

Cytogenetic: Xp11.22-11.21 X: 53222149-55057617 (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	Feb 13, 2023	Jun 9, 2024	Nov 27, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NC_000023.10:g.(?_53222149)_(55057617_?)del

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.
FGD1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	340	544
IQSEC2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1191	1350
KDM5C		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	771	939
PHF8		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	208	359
SMC1A		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	926	1094
HSD17B10		No evidence available	No evidence available	GRCh38 GRCh37	166	325
HUWE1		No evidence available	No evidence available	GRCh38 GRCh37	1390	1636
ALAS2		-	-	GRCh38 GRCh37	199	409
APEX2		-	-	GRCh38 GRCh37	30	163
FAM120C		-	-	GRCh38 GRCh37	30	180

There are 11 more genes affected by this variant. See the full set of genes in Variation Viewer (GRCh37) and ClinGen Dosage Sensitivity Map.

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)	criteria provided, single submitter	Nov 27, 2023	RCV003109486.5

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 (Nov 27, 2023)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Congenital muscular hypertrophy-cerebral syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV003791463.3 First in ClinVar: Feb 13, 2023 Last updated: Jun 09, 2024	Publications: PubMed (6) PubMed: 26386245‚ 27334371‚ 28166369‚ 28548707‚ 31334757‚ 31602316 Comment: A gross deletion of the genomic region encompassing the full coding sequence of the SMC1A gene has been identified. Loss-of-function variants in SMC1A are known … (more) A gross deletion of the genomic region encompassing the full coding sequence of the SMC1A gene has been identified. Loss-of-function variants in SMC1A are known to be pathogenic (PMID: 26386245, 27334371, 28166369, 28548707, 31334757). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with clinical features of SMC1A-related conditions (PMID: 31602316). For these reasons, this variant has been classified as Pathogenic. (less)

Comment:

A gross deletion of the genomic region encompassing the full coding sequence of the SMC1A gene has been identified. Loss-of-function variants in SMC1A are known to be pathogenic (PMID: 26386245, 27334371, 28166369, 28548707, 31334757). The boundaries of this event are unknown as they extend beyond the assayed region for this gene and therefore may encompass additional genes. A similar copy number variant has been observed in individual(s) with clinical features of SMC1A-related conditions (PMID: 31602316). For these reasons, this variant has been classified as Pathogenic.

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
A large data resource of genomic copy number variation across neurodevelopmental disorders.	Zarrei M	NPJ genomic medicine	2019	PMID: 31602316
Cohesin complex-associated holoprosencephaly.	Kruszka P	Brain : a journal of neurology	2019	PMID: 31334757
Phenotypes and genotypes in individuals with SMC1A variants.	Huisman S	American journal of medical genetics. Part A	2017	PMID: 28548707
Heterozygous truncation mutations of the SMC1A gene cause a severe early onset epilepsy with cluster seizures in females: Detailed phenotyping of 10 new cases.	Symonds JD	Epilepsia	2017	PMID: 28166369
Mutations in HECW2 are associated with intellectual disability and epilepsy.	Halvardson J	Journal of medical genetics	2016	PMID: 27334371
Novel SMC1A frameshift mutations in children with developmental delay and epilepsy.	Goldstein JH	European journal of medical genetics	2015	PMID: 26386245

Text-mined citations for this variant ...

Record last updated Sep 30, 2024

ClinVar Genomic variation as it relates to human health

NC_000023.10:g.(?_53222149)_(55057617_?)del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...