This sequence change creates a premature translational stop signal (p.Gln50*) in the DNAJC21 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAJC21 are known to be pathogenic (PMID: 27346687, 28062395). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNAJC21-related conditions. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic
- Review status:
- criteria provided, single submitter
- Submissions:
- 2
- First in ClinVar:
- Feb 11, 2022
- Most recent Submission:
- Mar 28, 2022
- Last evaluated:
- Dec 8, 2021
- Accession:
- VCV001339571.2
- Variation ID:
- 1339571
- Description:
- single nucleotide variant
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NM_001012339.3(DNAJC21):c.148C>T (p.Gln50Ter)
- Allele ID
- 1330717
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 5p13.2
- Genomic location
- 5: 34933865 (GRCh38) GRCh38 UCSC
- 5: 34933970 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001012339.3:c.148C>T MANE Select NP_001012339.2:p.Gln50Ter nonsense NM_001348420.2:c.148C>T NP_001335349.1:p.Gln50Ter nonsense NM_194283.4:c.148C>T NP_919259.3:p.Gln50Ter nonsense NC_000005.10:g.34933865C>T NC_000005.9:g.34933970C>T NG_052822.1:g.9326C>T LRG_1214:g.9326C>T LRG_1214t1:c.148C>T LRG_1214p1:p.Gln50Ter - Protein change
- Q50*
- Other names
- -
- Canonical SPDI
- NC_000005.10:34933864:C:T
- Functional consequence
- functionally_abnormal [Sequence Ontology SO:0002218]
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic | 1 | criteria provided, single submitter | Dec 8, 2021 | RCV001869834.1 | |
| Pathogenic | 1 | no assertion criteria provided | Feb 8, 2022 | RCV001824280.1 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| DNAJC21 | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
209 | 236 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Dec 08, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV002195890.1
First in ClinVar: Mar 28, 2022 Last updated: Mar 28, 2022 |
Comment:
This sequence change creates a premature translational stop signal (p.Gln50*) in the DNAJC21 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Gln50*) in the DNAJC21 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DNAJC21 are known to be pathogenic (PMID: 27346687, 28062395). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DNAJC21-related conditions. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Feb 08, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Bone marrow failure syndrome 3
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
|
Center of Genomic Medicine,University of Medicine and Pharmacy Victor Babes Timisoara
Accession: SCV002073732.1
First in ClinVar: Feb 11, 2022 Last updated: Feb 11, 2022 |
Comment:
This null variant has been observed in compound heterozigosity with another pathogenic variant in a patient with Bone marrow failure syndrome 3. PVS2 Very Strong: … (more)
This null variant has been observed in compound heterozigosity with another pathogenic variant in a patient with Bone marrow failure syndrome 3. PVS2 Very Strong: Null variant (nonsense), in gene DNAJC21 for which loss-of-function is a known mechanism of disease, associated with Bone marrow failure syndrome 3. PM2 Strong: Using strength Strong because the position is highly conserved (phyloP100way = 7.35 is greater than 7.2). Variant not found in gnomAD exomes. Variant not found in gnomAD genomes (good gnomAD genomes coverage = 31.1). PP3 Supporting: Pathogenic computational verdict based on 5 pathogenic predictions from BayesDel_addAF, DANN, EIGEN, FATHMM-MKL and MutationTaster vs no benign predictions. (less)
Clinical Features:
Retinal dystrophy (present) , Failure to thrive (present) , Fetal growth restriction (present) , Myopia (present) , Cryptorchidism (present) , Pancytopenia (present) , Joint hypermobility … (more)
Retinal dystrophy (present) , Failure to thrive (present) , Fetal growth restriction (present) , Myopia (present) , Cryptorchidism (present) , Pancytopenia (present) , Joint hypermobility (present) , Enamel hypoplasia (present) , Eczema (present) , Microcephaly (present) (less)
Zygosity: 1 Compound Heterozygote
Age: 0-9 years
Sex: male
Ethnicity/Population group: European
Method: WGS
Testing laboratory: Invitae
Date variant was reported to submitter: 2021-11-04
Testing laboratory interpretation: Pathogenic
|
Functional evidence
Help| Functional consequence | Method | Result | Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
functionally_abnormal
|
Center of Genomic Medicine,University of Medicine and Pharmacy Victor Babes Timisoara
Accession: SCV002073732.1
Submitted: (Feb 08, 2022)
|
|
Citations for this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
Record last updated Apr 25, 2022