ClinVar Genomic variation as it relates to human health
NM_001353214.3(DYM):c.2043del (p.Lys681fs)
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.
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.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001353214.3(DYM):c.2043del (p.Lys681fs)
Variation ID: 3191 Accession: VCV000003191.8
- Type and length
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Deletion, 1 bp
- Location
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Cytogenetic: 18q21.1 18: 49044187 (GRCh38) [ NCBI UCSC ] 18: 46570557 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Jul 16, 2015 Feb 14, 2024 Oct 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001353214.3:c.2043del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001340143.1:p.Lys681fs frameshift NM_001353210.3:c.1875del NP_001340139.1:p.Lys625fs frameshift NM_001353211.3:c.1875del NP_001340140.1:p.Lys625fs frameshift NM_001353212.3:c.2040del NP_001340141.1:p.Lys680fs frameshift NM_001353213.3:c.2040del NP_001340142.1:p.Lys680fs frameshift NM_001353215.3:c.1860del NP_001340144.1:p.Lys620fs frameshift NM_001353216.3:c.1695del NP_001340145.1:p.Lys565fs frameshift NM_001374428.1:c.2043del NP_001361357.1:p.Lys681fs frameshift NM_001374429.1:c.2037del NP_001361358.1:p.Lys679fs frameshift NM_001374430.1:c.*2del NP_001361359.1:p.Ter712= no sequence alteration NM_001374431.1:c.1929del NP_001361360.1:p.Lys643fs frameshift NM_001374432.1:c.1917del NP_001361361.1:p.Lys639fs frameshift NM_001374433.1:c.*2del NP_001361362.1:p.Ter657= no sequence alteration NM_001374434.1:c.1764del NP_001361363.1:p.Lys588fs frameshift NM_001374435.1:c.1761del NP_001361364.1:p.Lys587fs frameshift NM_001374436.1:c.1752del NP_001361365.1:p.Lys584fs frameshift NM_001374437.1:c.1695del NP_001361366.1:p.Lys565fs frameshift NM_001374438.1:c.1692del NP_001361367.1:p.Lys564fs frameshift NM_001374439.1:c.1689del NP_001361368.1:p.Lys563fs frameshift NM_001374440.1:c.1650del NP_001361369.1:p.Lys550fs frameshift NM_001374441.1:c.1473del NP_001361370.1:p.Lys491fs frameshift NM_001374442.1:c.1308del NP_001361371.1:p.Lys436fs frameshift NM_001374443.1:c.1305del NP_001361372.1:p.Lys435fs frameshift NM_001374444.1:c.1125del NP_001361373.1:p.Lys375fs frameshift NM_017653.6:c.1878del NP_060123.3:p.Lys626fs frameshift NC_000018.10:g.49044189del NC_000018.9:g.46570559del NG_009239.2:g.421547del - Protein change
- K626fs, K565fs, K620fs, K625fs, K680fs, K681fs, K375fs, K435fs, K436fs, K491fs, K550fs, K563fs, K564fs, K584fs, K587fs, K588fs, K639fs, K643fs, K679fs
- Other names
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- Canonical SPDI
- NC_000018.10:49044186:TTT:TT
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe 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.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
- Comment on variant
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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DYM | - | - |
GRCh38 GRCh37 |
298 | 377 | |
DYM-AS1 | - | - | - | GRCh38 | - | 40 |
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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
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May 22, 2022 | RCV000003342.8 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Oct 8, 2023 | RCV001851609.4 |
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
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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. |
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Pathogenic
(Jul 10, 2018)
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criteria provided, single submitter
Method: clinical testing
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Dyggve-Melchior-Clausen syndrome
Affected status: yes
Allele origin:
inherited
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Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000966172.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
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Likely pathogenic
(Oct 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002284919.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change results in a frameshift in the DYM gene (p.Lys626Asnfs*94). While this is not anticipated to result in nonsense mediated decay, it is … (more)
This sequence change results in a frameshift in the DYM gene (p.Lys626Asnfs*94). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the DYM protein and extend the protein by 49 additional amino acid residues. This variant is present in population databases (no rsID available, gnomAD 0.02%). This frameshift has been observed in individuals with clinical features of Dyggve-Melchior-Clausen disease (PMID: 12554689, 22090722; Invitae). This variant is also known as c.1877delA. ClinVar contains an entry for this variant (Variation ID: 3191). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(May 22, 2022)
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criteria provided, single submitter
Method: clinical testing
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Dyggve-Melchior-Clausen syndrome
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002521074.1
First in ClinVar: Jun 03, 2022 Last updated: Jun 03, 2022 |
Comment:
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Frameshift: predicted to result in a loss … (more)
The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Frameshift: predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID: 12554689). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Spondylometaphyseal dysplasia (present) , Severe short stature (present) , Abnormality of the skeletal system (present)
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Pathogenic
(Feb 01, 2003)
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no assertion criteria provided
Method: literature only
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DYGGVE-MELCHIOR-CLAUSEN DISEASE
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000023500.2
First in ClinVar: Apr 04, 2013 Last updated: Jul 16, 2015 |
Comment on evidence:
In 3 consanguineous Moroccan families with Dyggve-Melchior-Clausen disease (DMC; 223800), El Ghouzzi et al. (2003) identified homozygous deletion of a single basepair in exon 17 … (more)
In 3 consanguineous Moroccan families with Dyggve-Melchior-Clausen disease (DMC; 223800), El Ghouzzi et al. (2003) identified homozygous deletion of a single basepair in exon 17 of the DYM gene (1877delA) in all affected children. The deletion was found in compound heterozygosity with a nonsense mutation in an additional nonconsanguineous Moroccan family. The frameshift mutation predicted a 49-amino acid extension of the DYM protein with the last 93 amino acids being missense (K626N+92aa to stop). (less)
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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. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A recurrent mutation in Moroccan patients with Dyggve-Melchior-Clausen syndrome: Report of a new case and review. | Elalaoui SC | Indian journal of human genetics | 2011 | PMID: 22090722 |
Mutations in a novel gene Dymeclin (FLJ20071) are responsible for Dyggve-Melchior-Clausen syndrome. | El Ghouzzi V | Human molecular genetics | 2003 | PMID: 12554689 |
Text-mined citations for rs1471488189 ...
HelpRecord last updated Sep 29, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.
ClinGen staff contributed the HGVS expression for this variant.