ClinVar Genomic variation as it relates to human health
NM_201525.4(ADGRG1):c.1010dup (p.Gln338fs)
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_201525.4(ADGRG1):c.1010dup (p.Gln338fs)
Variation ID: 1878521 Accession: VCV001878521.2
- Type and length
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Duplication, 1 bp
- Location
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Cytogenetic: 16q21 16: 57655984-57655985 (GRCh38) [ NCBI UCSC ] 16: 57689896-57689897 (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 Jan 21, 2023 Oct 28, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_201525.4:c.1010dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_958933.1:p.Gln338fs frameshift NM_001145770.3:c.1010dup NP_001139242.1:p.Gln338fs frameshift NM_001145771.3:c.1010dup NP_001139243.1:p.Gln338fs frameshift NM_001145772.3:c.1010dup NP_001139244.1:p.Gln338fs frameshift NM_001145773.3:c.1025dup NP_001139245.1:p.Gln343fs frameshift NM_001145774.3:c.1010dup NP_001139246.1:p.Gln338fs frameshift NM_001290142.2:c.500dup NP_001277071.1:p.Gln168fs frameshift NM_001290143.2:c.485dup NP_001277072.1:p.Gln163fs frameshift NM_001290144.2:c.485dup NP_001277073.1:p.Gln163fs frameshift NM_001370428.1:c.1010dup NP_001357357.1:p.Gln338fs frameshift NM_001370429.1:c.1010dup NP_001357358.1:p.Gln338fs frameshift NM_001370430.1:c.1010dup NP_001357359.1:p.Gln338fs frameshift NM_001370431.1:c.1010dup NP_001357360.1:p.Gln338fs frameshift NM_001370432.1:c.1010dup NP_001357361.1:p.Gln338fs frameshift NM_001370433.1:c.1025dup NP_001357362.1:p.Gln343fs frameshift NM_001370434.1:c.1010dup NP_001357363.1:p.Gln338fs frameshift NM_001370435.1:c.1010dup NP_001357364.1:p.Gln338fs frameshift NM_001370436.1:c.1010dup NP_001357365.1:p.Gln338fs frameshift NM_001370437.1:c.1010dup NP_001357366.1:p.Gln338fs frameshift NM_001370438.1:c.1010dup NP_001357367.1:p.Gln338fs frameshift NM_001370439.1:c.1010dup NP_001357368.1:p.Gln338fs frameshift NM_001370440.1:c.1010dup NP_001357369.1:p.Gln338fs frameshift NM_001370441.1:c.1010dup NP_001357370.1:p.Gln338fs frameshift NM_001370442.1:c.854dup NP_001357371.1:p.Gln286fs frameshift NM_001370451.1:c.485dup NP_001357380.1:p.Gln163fs frameshift NM_001370453.1:c.485dup NP_001357382.1:p.Gln163fs frameshift NM_001370454.1:c.485dup NP_001357383.1:p.Gln163fs frameshift NM_005682.7:c.1010dup NP_005673.3:p.Gln338fs frameshift NM_201524.4:c.1010dup NP_958932.1:p.Gln338fs frameshift NC_000016.10:g.57655985dup NC_000016.9:g.57689897dup NG_011643.1:g.40988dup - Protein change
- Q163fs, Q168fs, Q286fs, Q338fs, Q343fs
- Other names
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- Canonical SPDI
- NC_000016.10:57655984:T: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
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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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ADGRG1 | - | - |
GRCh38 GRCh37 |
935 | 962 |
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
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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, single submitter
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- | RCV002510612.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
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- | RCV003340499.2 |
Submissions - Germline
Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
(-)
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criteria provided, single submitter
Method: clinical testing
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Bilateral frontoparietal polymicrogyria
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820093.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
The frameshift duplication p.Q338Tfs*14 in ADGRG1 (NM_005682.7) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The … (more)
The frameshift duplication p.Q338Tfs*14 in ADGRG1 (NM_005682.7) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Q338Tfs*14 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. (less)
Clinical Features:
Hypotonia (present) , Global developmental delay (present)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Polymicrogyria, bilateral perisylvian, autosomal recessive
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047876.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The c.1010dup (p.Gln338ThrfsTer14) frameshift variant in ADGRG1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. … (more)
The c.1010dup (p.Gln338ThrfsTer14) frameshift variant in ADGRG1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Gln338ThrfsTer14 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant causes a frameshift starting with codon Glutamine 338, changes this amino acid to Threonine residue, and creates a premature Stop codon at position 14 of the new reading frame, denoted p.Gln338ThrfsTer14. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic. (less)
Clinical Features:
Bilateral tonic-clonic seizure (present)
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Pathogenic
(Sep 12, 2023)
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no assertion criteria provided
Method: literature only
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CORTICAL DYSPLASIA, COMPLEX, WITH OTHER BRAIN MALFORMATIONS 14A (BILATERAL FRONTOPARIETAL)
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV004035033.2
First in ClinVar: Sep 16, 2023 Last updated: Sep 23, 2023 |
Comment on evidence:
For discussion of the 1-bp duplication in exon 8 of the ADGRG1 gene (c.1010dupT), resulting in a frameshift and premature termination (Gln338ThrfsTer13), that was found … (more)
For discussion of the 1-bp duplication in exon 8 of the ADGRG1 gene (c.1010dupT), resulting in a frameshift and premature termination (Gln338ThrfsTer13), that was found in compound heterozygous state in a patient with complex cortical dysplasia with other brain malformations-14A (bilateral frontoparietal) (CDCBM14A; 606854) by Jha et al. (2022), see 604110.0013. (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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Two Novel Compound Heterozygous ADGRG1/GPR56 Mutations Associated with Diffuse Cerebral Polymicrogyria. | Jha R | Journal of pediatric genetics | 2020 | PMID: 35186395 |
Text-mined citations for this variant ...
HelpRecord last updated Apr 06, 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.