VCV000044273.45 - ClinVar

NM_001927.4(DES):c.897+4_897+5del

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.

(17)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001927.4(DES):c.897+4_897+5del

Variation ID: 44273 Accession: VCV000044273.45

Type and length

Deletion, 2 bp

Location

Cytogenetic: 2q35 2: 219420659-219420660 (GRCh38) [ NCBI UCSC ] 2: 220285381-220285382 (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	May 29, 2016	Oct 20, 2024	Jun 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001927.4:c.897+4_897+5del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NC_000002.12:g.219420660_219420661del
NC_000002.11:g.220285382_220285383del
NG_008043.1:g.7284_7285del
LRG_380:g.7284_7285del
LRG_380t1:c.897+4_897+5del

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000002.12:219420658:GGG:G

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.

0.00359 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA133882 dbSNP: rs397516699 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.
DES		-	-	GRCh38 GRCh37	1062	1108

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 specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Feb 13, 2023	RCV000037255.20
Myofibrillar Myopathy, Dominant	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000298076.12
Scapuloperoneal weakness	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000304469.12
Dilated Cardiomyopathy, Dominant	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000352919.12
Desmin-related myofibrillar myopathy	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Jan 17, 2024	RCV000462365.21
Cardiomyopathy	Benign (1)	criteria provided, single submitter	Jul 30, 2018	RCV000770170.10
Dilated cardiomyopathy 1I	Likely benign (1)	criteria provided, single submitter	-	RCV001258319.9
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Mar 13, 2020	RCV002444477.9
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Jun 1, 2024	RCV001610325.22
DES-related disorder	Likely benign (1)	no assertion criteria provided	Jan 30, 2020	RCV003924916.2
Desmin-related myofibrillar myopathy Dilated cardiomyopathy 1I Neurogenic scapuloperoneal syndrome, Kaeser type	Benign (1)	criteria provided, single submitter	Jul 26, 2021	RCV002482986.8
click to load more click to collapse

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.
Benign (Mar 19, 2015)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060912.5 First in ClinVar: May 03, 2013 Last updated: May 29, 2016	Comment: c.897+4_897+5delGG in intron 4 of DES: This variant is not expected to have clin ical significance because it has been identified in 1.6% (260/16508) of … (more) c.897+4_897+5delGG in intron 4 of DES: This variant is not expected to have clin ical significance because it has been identified in 1.6% (260/16508) of South As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs397516699). (less) Number of individuals with the variant: 4
Benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Desmin-related myofibrillar myopathy Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001136222.1 First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020
Benign (Jul 30, 2018)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV000901597.2 First in ClinVar: May 06, 2019 Last updated: May 31, 2020
Benign (Sep 01, 2020)	criteria provided, single submitter (Athena Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Athena Diagnostics Accession: SCV001475074.2 First in ClinVar: Jan 26, 2021 Last updated: Sep 19, 2021	Publications: PubMed (1) PubMed: 20474083
Benign (Jul 26, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Neurogenic scapuloperoneal syndrome, Kaeser type Desmin-related myofibrillar myopathy Dilated cardiomyopathy 1I Affected status: unknown Allele origin: unknown	Fulgent Genetics, Fulgent Genetics Accession: SCV002804324.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022
Benign (Feb 13, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV003844623.1 First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Dilated Cardiomyopathy, Dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427719.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Desminopathy Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427720.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Myofibrillar Myopathy, Dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427718.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Neurogenic Scapuloperoneal Syndrome Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427721.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Mar 21, 2017)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000700600.2 First in ClinVar: May 29, 2016 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES Number of individuals with the variant: 2 Sex: mixed
Likely benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Dilated cardiomyopathy 1I (Autosomal dominant inheritance) Affected status: yes Allele origin: germline	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard Accession: SCV001435287.1 First in ClinVar: Oct 03, 2020 Last updated: Oct 03, 2020	Publications: PubMed (1) PubMed: 20474083 Comment: The heterozygous c.897+4_897+5delGG variant in DES has been identified in an individual with dilated cardiomyopathy (PMID: 20474083), but has also been identified in >1% of … (more) The heterozygous c.897+4_897+5delGG variant in DES has been identified in an individual with dilated cardiomyopathy (PMID: 20474083), but has also been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant dilated cardiomyopathy. (less)
Benign (Oct 24, 2016)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001841958.1 First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021	Comment: This variant is associated with the following publications: (PMID: 33250842, 27535533, 20474083)
Benign (Jan 17, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Desmin-related myofibrillar myopathy Desmin-related myofibrillar myopathy Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000562345.8 First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024
Benign (Mar 13, 2020)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002682111.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Publications: PubMed (1) PubMed: 20474083 Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Jun 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV002821029.14 First in ClinVar: Jan 21, 2023 Last updated: Oct 20, 2024	Comment: DES: BP4, BS1, BS2 Number of individuals with the variant: 10
Likely benign (Jan 30, 2020)	no assertion criteria provided Method: clinical testing	DES-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004743654.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
click to load more click to collapse

Comment:

c.897+4_897+5delGG in intron 4 of DES: This variant is not expected to have clin ical significance because it has been identified in 1.6% (260/16508) of South As ian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinst itute.org; dbSNP rs397516699).

Comment:

The heterozygous c.897+4_897+5delGG variant in DES has been identified in an individual with dilated cardiomyopathy (PMID: 20474083), but has also been identified in >1% of South Asian chromosomes and 4 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for autosomal dominant dilated cardiomyopathy.

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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 novel custom resequencing array for dilated cardiomyopathy.	Zimmerman RS	Genetics in medicine : official journal of the American College of Medical Genetics	2010	PMID: 20474083
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES	-	-	-	-

Text-mined citations for rs397516699 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 03, 2024

ClinVar Genomic variation as it relates to human health

NM_001927.4(DES):c.897+4_897+5del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs397516699 ...