ClinVar Genomic variation as it relates to human health
NM_001012339.3(DNAJC21):c.983+1G>A
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.
Pathogenic(1); Likely pathogenic(3); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001012339.3(DNAJC21):c.983+1G>A
Variation ID: 222066 Accession: VCV000222066.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5p13.2 5: 34941184 (GRCh38) [ NCBI UCSC ] 5: 34941289 (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 24, 2016 Jan 26, 2024 Oct 31, 2022 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001012339.3:c.983+1G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice donor NM_001348420.2:c.983+1G>A splice donor NM_194283.3:c.983+1G>A NM_194283.4:c.983+1G>A splice donor NC_000005.10:g.34941184G>A NC_000005.9:g.34941289G>A NG_052822.1:g.16645G>A LRG_1214:g.16645G>A LRG_1214t1:c.983+1G>A - Protein change
- Other names
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- Canonical SPDI
- NC_000005.10:34941183:G: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.
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
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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DNAJC21 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
327 | 382 |
Conditions - Germline
Condition
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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 (1) |
no assertion criteria provided
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Dec 17, 2015 | RCV000235793.9 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Oct 19, 2020 | RCV000784914.13 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 31, 2022 | RCV001818506.13 | |
Likely pathogenic (1) |
criteria provided, single submitter
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May 4, 2022 | RCV002247638.9 |
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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Uncertain significance
(Jan 01, 2019)
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criteria provided, single submitter
Method: clinical testing
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Bone marrow failure syndrome 3
Affected status: yes
Allele origin:
inherited
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000923455.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
Number of individuals with the variant: 1
Geographic origin: Iran
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Pathogenic
(Nov 19, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002072135.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
Comment:
DNA sequence analysis of the DNAJC21 gene demonstrated a sequence change in the canonical splice donor site of intron 7, c.983+1G>A. This sequence change has … (more)
DNA sequence analysis of the DNAJC21 gene demonstrated a sequence change in the canonical splice donor site of intron 7, c.983+1G>A. This sequence change has been described in EXAC database with a low population frequency of 0.004% (dbSNP rs368148362). This particular sequence change does not appear to have been described in the literature in other patients with DNAJC21-related disorders, however a different pathogenic sequence change affecting the same nucleotide (c.983+1G>T) has been described in a patient with bone marrow failure syndrome in a homozygous state (PMID: 27346687). This pathogenic sequence change is predicted to affect normal splicing of the DNAJC21 gene and result in an abnormal protein which may be degraded. (less)
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Likely pathogenic
(May 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Shwachman-Diamond syndrome 1
Affected status: unknown
Allele origin:
germline
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Mendelics
Accession: SCV002516310.1
First in ClinVar: May 28, 2022 Last updated: May 28, 2022 |
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Likely pathogenic
(Oct 19, 2020)
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criteria provided, single submitter
Method: clinical testing
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Bone marrow failure syndrome 3
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Victorian Clinical Genetics Services, Murdoch Childrens Research Institute
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002768436.1
First in ClinVar: Dec 24, 2022 Last updated: Dec 24, 2022 |
Comment:
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of … (more)
Based on the classification scheme VCGS_Germline_v1.1.1, this variant is classified as likely pathogenic. Following criteria are met: 0102 - Loss-of-function is a known mechanism of disease for this gene. (N) 0106 - This gene is known to be associated with autosomal recessive disease. (N) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available) (intron 7 of 11). (P) 0251 - Variant is heterozygous. (N) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (16 heterozygotes, 0 homozygotes). (P) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (P) 0703 - Comparable variants have moderate previous evidence for pathogenicity. Alternative nucleotide change at the same location has been reported to be pathogenic (ClinVar, PMID: 27346687) (P) 0803 - Low previous evidence of pathogenicity in unrelated individuals as pathogenic (ClinVar, PMID: 29146883), and also once as VUS (ClinVar). (P) 0905 - No segregation evidence has been identified for this variant. (N) 1007 - No published functional evidence has been identified for this variant. (N) 1205 - Variant is maternally inherited. (N) Legend: (P) - Pathogenic, (N) - Neutral, (B) - Benign (less)
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Likely pathogenic
(Oct 31, 2022)
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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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Invitae
Accession: SCV002256265.2
First in ClinVar: Mar 28, 2022 Last updated: Feb 07, 2023 |
Comment:
This sequence change affects a donor splice site in intron 7 of the DNAJC21 gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects a donor splice site in intron 7 of the DNAJC21 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DNAJC21 are known to be pathogenic (PMID: 27346687, 28062395). This variant is present in population databases (rs368148362, gnomAD 0.006%). Disruption of this splice site has been observed in individual(s) with clinical features of DNAJC21-related conditions (PMID: 27346687). ClinVar contains an entry for this variant (Variation ID: 222066). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
(Dec 17, 2015)
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no assertion criteria provided
Method: research
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Inherited bone marrow failure syndrome
Affected status: yes
Allele origin:
unknown
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Bone Marrow Failure laboratory, Queen Mary University London
Accession: SCV000257533.1
First in ClinVar: Jul 24, 2016 Last updated: Jul 24, 2016 |
Number of individuals with the variant: 1
Family history: no
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Pathogenic
(Feb 15, 2023)
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no assertion criteria provided
Method: clinical testing
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Bone marrow failure syndrome 3
Affected status: yes
Allele origin:
germline
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Istanbul Faculty of Medicine, Istanbul University
Accession: SCV004015015.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Number of individuals with the variant: 4
Clinical Features:
Anemia (present) , Thrombocytopenia (present) , Short stature (present) , Amelogenesis imperfecta (present)
Family history: yes
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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 landscape of germ line mutations in a cohort of inherited bone marrow failure patients. | Bluteau O | Blood | 2018 | PMID: 29146883 |
Biallelic mutations in DNAJC21 cause Shwachman-Diamond syndrome. | Dhanraj S | Blood | 2017 | PMID: 28062395 |
DNAJC21 Mutations Link a Cancer-Prone Bone Marrow Failure Syndrome to Corruption in 60S Ribosome Subunit Maturation. | Tummala H | American journal of human genetics | 2016 | PMID: 27346687 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Text-mined citations for rs368148362 ...
HelpRecord last updated Feb 04, 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.