VCV000805917.1 - ClinVar

GRCh37/hg19 7q22.1-22.3(chr7:103354482-105407628)

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

GRCh37/hg19 7q22.1-22.3(chr7:103354482-105407628)

Variation ID: 805917 Accession: VCV000805917.1

Type and length

copy number loss, 2,053,147 bp

Location

Cytogenetic: 7q22.1-22.3 7: 103354482-105407628 (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	Jan 25, 2020	Jan 25, 2020	Feb 7, 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.
KMT2E		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	942	974
RELN		No evidence available	No evidence available	GRCh38 GRCh37	2713	3544
ATXN7L1	-	-	-	GRCh38 GRCh37	52	79
LHFPL3		-	-	GRCh38 GRCh37	15	44
ORC5		-	-	GRCh38 GRCh37	23	45
PUS7		-	-	GRCh38 GRCh37	93	125
RINT1		-	-	GRCh38 GRCh37	1132	1484
SRPK2		-	-	GRCh38 GRCh37	43	79

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.
See cases	Likely pathogenic (1)	no assertion criteria provided	Feb 7, 2019	RCV000993742.2

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 (Feb 07, 2019)	no assertion criteria provided Method: research	See cases (Autosomal dominant inheritance) Affected status: yes Allele origin: de novo	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV001146931.1 First in ClinVar: Jan 25, 2020 Last updated: Jan 25, 2020	Comment: This heterozygous 2Mb deletion was identified by our study in one individual with intellectual disabilities, autism, and developmental delay. This deletion covers less than 15 … (more) This heterozygous 2Mb deletion was identified by our study in one individual with intellectual disabilities, autism, and developmental delay. This deletion covers less than 15 protein-coding RefSeq genes. The variant is assumed de novo in the individual, but maternity and paternity are not confirmed. This deletion overlaps with the KMT2E variant which is reported to have, at least 29 de novo variants, of which 15 have confirmed maternity and paternity. It is of note that loss of function of the KMT2E gene in autosomal dominant disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. (less) Clinical Features: Macrocephaly (present) , Developemental delay (present) , Autism (present) , Moderate intellectual disability (present) , Behavioral difficulties (present) , Hypotonia (present) , Flat nasal bridge … (more) Macrocephaly (present) , Developemental delay (present) , Autism (present) , Moderate intellectual disability (present) , Behavioral difficulties (present) , Hypotonia (present) , Flat nasal bridge (present) , Epicanthal folds (present) , Gastrostomy tube (present) , Strabismus (present) (less)

Comment:

This heterozygous 2Mb deletion was identified by our study in one individual with intellectual disabilities, autism, and developmental delay. This deletion covers less than 15 protein-coding RefSeq genes. The variant is assumed de novo in the individual, but maternity and paternity are not confirmed. This deletion overlaps with the KMT2E variant which is reported to have, at least 29 de novo variants, of which 15 have confirmed maternity and paternity. It is of note that loss of function of the KMT2E gene in autosomal dominant disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, although additional studies are required to fully establish its clinical significance, this variant is 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

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for this variant ...

Record last updated Mar 30, 2024

ClinVar Genomic variation as it relates to human health

GRCh37/hg19 7q22.1-22.3(chr7:103354482-105407628)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...