VCV001687716.1 - ClinVar

Single allele

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

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

Single allele

Variation ID: 1687716 Accession: VCV001687716.1

Type and length

Deletion, -

Location

Cytogenetic: 7q31.2-31.33 7: 114885745-124728629 (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	Jun 5, 2022	Jun 5, 2022	Sep 30, 2020

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.

complete gene deletion; Variation Ontology [ VariO:0169]

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.
CADPS2		No evidence available	No evidence available	GRCh38 GRCh37	99	189
MET		No evidence available	No evidence available	GRCh38 GRCh37	3774	3825
AASS		-	-	GRCh38 GRCh37	200	225
ANKRD7		-	-	GRCh38 GRCh37	14	39
ASB15		-	-	GRCh38 GRCh37	29	69
ASZ1		-	-	GRCh38 GRCh37	31	62
CAPZA2		-	-	GRCh38 GRCh37	20	54
CAV1		-	-	GRCh38 GRCh37	109	162
CAV2		-	-	GRCh38 GRCh37	15	45
CFTR		-	-	GRCh38 GRCh37	3825	5200

There are 30 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.
Delayed speech and language development	Likely pathogenic (1)	no assertion criteria provided	Sep 30, 2020	RCV002251690.1

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.
Likely pathogenic (Sep 30, 2020)	no assertion criteria provided Method: clinical testing	Delayed speech and language development (Autosomal dominant inheritance) Affected status: unknown, yes Allele origin: paternal, unknown	IU Genetic Testing Laboratories, Indiana University School of Medicine Accession: SCV002520684.1 First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022	Publications: PubMed (3) PubMed: 17330859‚ 32885567‚ 27075776 Comment: Deletions of this region have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. This deletion does not encompass the FOXP2 … (more) Deletions of this region have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. This deletion does not encompass the FOXP2 gene, which has been strongly associated with speech and language impairment and is included in the deleted region for the majority of published cases (PMID: 17330859). However, one recent case report describes a 4.7 Mb deletion downstream of FOXP2 in three family members presenting with variable speech, language and neurodevelopmental phenotypes; the proband in this family also had microcephaly, minor facial dysmorphism including prominent ears and wide mouth (PMID: 32885567). Another published case of a deletion in this region that does not include FOXP2, as well as a review of several overlapping 7q31 deletions listed in the DECIPHER database, suggested consistent features of delayed speech and language development (PMID: 27075776). It was hypothesized that the deletion results in a position effect on the nearby FOXP2 gene expression. (less) Observation 1: Clinical Features: Delayed speech and language development (present) , Global developmental delay (present) , Microcephaly (present) , Attention deficit hyperactivity disorder (present) Sex: female Testing laboratory: GTR Lab ID: 13521 Testing laboratory interpretation: Pathogenic Observation 2: Indication for testing: parental studies Sex: male Testing laboratory: GTR Lab ID: 13521

Comment:

Deletions of this region have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. This deletion does not encompass the FOXP2 gene, which has been strongly associated with speech and language impairment and is included in the deleted region for the majority of published cases (PMID: 17330859). However, one recent case report describes a 4.7 Mb deletion downstream of FOXP2 in three family members presenting with variable speech, language and neurodevelopmental phenotypes; the proband in this family also had microcephaly, minor facial dysmorphism including prominent ears and wide mouth (PMID: 32885567). Another published case of a deletion in this region that does not include FOXP2, as well as a review of several overlapping 7q31 deletions listed in the DECIPHER database, suggested consistent features of delayed speech and language development (PMID: 27075776). It was hypothesized that the deletion results in a position effect on the nearby FOXP2 gene expression.

Germline Functional Evidence

Functional Help The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence	Method Help A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter.	Result Help A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
complete gene deletion (VariO:0169)			IU Genetic Testing Laboratories, Indiana University School of Medicine Accession: SCV002520684.1	Publications PubMed (3)

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
7q31.2q31.31 deletion downstream of FOXP2 segregating in a family with speech and language disorder.	Rieger M	American journal of medical genetics. Part A	2020	PMID: 32885567
A de novo interstitial deletion of 7q31.2q31.31 identified in a girl with developmental delay and hearing loss.	Zhao J	American journal of medical genetics. Part C, Seminars in medical genetics	2016	PMID: 27075776
Deletion of 7q31.1 supports involvement of FOXP2 in language impairment: clinical report and review.	Lennon PA	American journal of medical genetics. Part A	2007	PMID: 17330859

Text-mined citations for this variant ...

Record last updated Jun 11, 2022

ClinVar Genomic variation as it relates to human health

Single allele

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...