ClinVar Genomic variation as it relates to human health
NM_001321075.3(DLG4):c.10_13del (p.Leu4fs)
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_001321075.3(DLG4):c.10_13del (p.Leu4fs)
Variation ID: 1805210 Accession: VCV001805210.3
- Type and length
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Deletion, 4 bp
- Location
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Cytogenetic: 17p13.1 17: 7217135-7217138 (GRCh38) [ NCBI UCSC ] 17: 7120454-7120457 (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 Dec 24, 2022 Feb 7, 2023 Jan 25, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001321075.3:c.10_13del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001308004.1:p.Leu4fs frameshift NM_001128827.4:c.10_13del NP_001122299.1:p.Leu4fs frameshift NM_001270447.2:c.-10_-7del 5 prime UTR NM_001321074.1:c.159+1103_159+1106del intron variant NM_001365.5:c.159+1103_159+1106del intron variant NC_000017.11:g.7217136_7217139del NC_000017.10:g.7120455_7120458del NG_007975.1:g.2303_2306del NG_008391.2:g.7913_7916del NG_008391.3:g.7912_7915del - Protein change
- L4fs
- Other names
- NM_001270447.2:c.-10_-7del
- Canonical SPDI
- NC_000017.11:7217134:AGAGA:A
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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
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The frequency of the allele represented by this VCV record.
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- Links
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
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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DLG4 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
141 | 303 | |
ACADVL | - | - |
GRCh38 GRCh37 |
1707 | 1912 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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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Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2023 | RCV002471628.10 |
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
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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
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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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Likely pathogenic
(Mar 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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Intellectual developmental disorder 62
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002769033.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known … (more)
Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with intellectual developmental disorder 62 (MIM#618793). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0204 - Variant is predicted to result in a truncated protein. It is located within the first 100 bases of the protein coding region, and therefore the nonsense-mediated decay efficiency is predicted to be lower (PMID: 27618451). (SP) 0219 - This variant is non-coding in alternative transcripts. This variant is located within an exon that is unique to only two RefSeq transcripts (NM_001321075.1 and NM_001128827.4). No pathogenic variants have been reported in this exon (ClinVar); however, gene expression dataset analysis has shown that this exon is expressed in several different human brain tissues (GTEx). (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0705 - No comparable premature termination variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by UDP-Broad trio exome sequencing). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign (less)
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Likely pathogenic
(Jan 25, 2023)
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criteria provided, single submitter
Method: curation
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Intellectual developmental disorder 62
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003761376.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The heterozygous p.Leu4ValfsTer2 variant in DLG4 was identified by our study in one individual with autism, dysmorphic facies, and seizures. Trio exome analysis showed this … (more)
The heterozygous p.Leu4ValfsTer2 variant in DLG4 was identified by our study in one individual with autism, dysmorphic facies, and seizures. Trio exome analysis showed this variant to be de novo. The p.Leu4ValfsTer2 variant in DLG4 has not been previously reported in individuals with autosomal dominant intellectual developmental disorder 62. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 4 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the DLG4 gene is strongly associated to autosomal dominant intellectual developmental disorder 62. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant intellectual developmental disorder 62. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Supporting, PM2_Supporting (Richards 2015). (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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The rules and impact of nonsense-mediated mRNA decay in human cancers. | Lindeboom RG | Nature genetics | 2016 | PMID: 27618451 |
Text-mined citations for this variant ...
HelpRecord last updated May 01, 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.