VCV000988915.4 - ClinVar

GRCh37/hg19 5q31.2(chr5:137754277-138994590)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.

Likely pathogenic

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

GRCh37/hg19 5q31.2(chr5:137754277-138994590)x1

Variation ID: 988915 Accession: VCV000988915.4

Type and length

copy number loss, 1,240,314 bp

Location

Cytogenetic: 5q31.2 5: 137754277-138994590 (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	Dec 19, 2020	Mar 4, 2023	Sep 4, 2019

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.
CTNNA1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2875	2934
DNAJC18	-	-	-	GRCh38 GRCh38 GRCh37	21	50
ECSCR		-	-	GRCh38 GRCh38 GRCh37	1	30
EGR1		-	-	GRCh38 GRCh37	11	33
ETF1		-	-	GRCh38 GRCh37	1	19
HSPA9		-	-	GRCh38 GRCh37	61	80
KDM3B		-	-	GRCh38 GRCh37	246	281
LRRTM2		-	-	GRCh38 GRCh37	-	49
MATR3		-	-	GRCh38 GRCh37	426	549
MZB1		-	-	GRCh38 GRCh37	10	42

There are 9 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.
not provided	Likely pathogenic (1)	criteria provided, single submitter	Sep 4, 2019	RCV001270645.4

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.
Likely pathogenic (Sep 04, 2019)	criteria provided, single submitter (ICSL CNVClassificationCriteria Aug2020) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Illumina Laboratory Services, Illumina Accession: SCV001451376.2 First in ClinVar: Dec 19, 2020 Last updated: Mar 04, 2023	Publications: PubMed (2) PubMed: 17506096‚ 23326251 Comment: This CNV is a 1.2 Mb deletion of 5q31.2, on chromosome 5, (seq[GRCh37]del(5)(q31.2); chr5:g.137754277_138994590del), of unknown inheritance. This CNV constitutes a loss encompassing 22 genes … (more) This CNV is a 1.2 Mb deletion of 5q31.2, on chromosome 5, (seq[GRCh37]del(5)(q31.2); chr5:g.137754277_138994590del), of unknown inheritance. This CNV constitutes a loss encompassing 22 genes that has not been reported in controls. Similar CNVs have been reported in two individuals with developmental delay and delayed speech. Kleffman et al. (2012) reported a 0.9 Mb deletion, fully encompassed within this CNV, in a seven-year-old male presenting with mild developmental delay, delayed speech, borderline short stature, postnatal microcephaly, and mild dysmorphic features that included mild microretrognathia. A larger CNV of 1.8 Mb, fully encompassing the CNV of interest, was reported in a one-year old female with delayed speech, developmental delay, abnormal cry and dysmorphic features which included upslanting palpebral fissures and microretrognathia (Mosca et al. 2007). Based on the available evidence, this CNV is classified as likely pathogenic. (less)

Comment:

This CNV is a 1.2 Mb deletion of 5q31.2, on chromosome 5, (seq[GRCh37]del(5)(q31.2); chr5:g.137754277_138994590del), of unknown inheritance. This CNV constitutes a loss encompassing 22 genes that has not been reported in controls. Similar CNVs have been reported in two individuals with developmental delay and delayed speech. Kleffman et al. (2012) reported a 0.9 Mb deletion, fully encompassed within this CNV, in a seven-year-old male presenting with mild developmental delay, delayed speech, borderline short stature, postnatal microcephaly, and mild dysmorphic features that included mild microretrognathia. A larger CNV of 1.8 Mb, fully encompassing the CNV of interest, was reported in a one-year old female with delayed speech, developmental delay, abnormal cry and dysmorphic features which included upslanting palpebral fissures and microretrognathia (Mosca et al. 2007). Based on the available evidence, this CNV is classified as likely 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
5q31 Microdeletions: Definition of a Critical Region and Analysis of LRRTM2, a Candidate Gene for Intellectual Disability.	Kleffmann W	Molecular syndromology	2012	PMID: 23326251
Fortuitous FISH diagnosis of an interstitial microdeletion (5)(q31.1q31.2) in a girl suspected to present a cri-du-chat syndrome.	Mosca AL	American journal of medical genetics. Part A	2007	PMID: 17506096

Text-mined citations for this variant ...

Record last updated Apr 09, 2023

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 5q31.2(chr5:137754277-138994590)x1

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...