The c.1648C>T;p.(Arg550*) variant creates a premature translational stop signal in the SEC23B gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 20015893; PMID: 22208203) - PS4. The variant is present at low allele frequencies population databases (rs199939108 – gnomAD 0.0005657%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg550*) was detected in trans with a pathogenic variant (PMID: 20015893) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
ClinVar Genomic variation as it relates to human health
NM_006363.6(SEC23B):c.1648C>T (p.Arg550Ter)
Germline
Classification
Help
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.
(7)
Help
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
7
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006363.6(SEC23B):c.1648C>T (p.Arg550Ter)
Variation ID: 167668 Accession: VCV000167668.14
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p11.23 20: 18543155 (GRCh38) [ NCBI UCSC ] 20: 18523799 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jun 29, 2015 Oct 8, 2024 Jan 31, 2024 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006363.6:c.1648C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006354.2:p.Arg550Ter nonsense NM_001172745.3:c.1648C>T NP_001166216.1:p.Arg550Ter nonsense NM_001172746.3:c.1594C>T NP_001166217.1:p.Arg532Ter nonsense NM_006363.4:c.1648C>T NM_032985.6:c.1648C>T NP_116780.1:p.Arg550Ter nonsense NM_032986.5:c.1648C>T NP_116781.1:p.Arg550Ter nonsense NC_000020.11:g.18543155C>T NC_000020.10:g.18523799C>T NG_016281.2:g.40674C>T LRG_1134:g.40674C>T LRG_1134t1:c.1648C>T LRG_1134p1:p.Arg550Ter - Protein change
- R550*, R532*
- Other names
- -
- Canonical SPDI
- NC_000020.11:18543154:C:T
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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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD), exomes 0.00006
Exome Aggregation Consortium (ExAC) 0.00007
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
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. |
|||
| SEC23B | - | - |
GRCh38 GRCh37 |
586 | 702 | |
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2024 | RCV000153929.10 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 9, 2023 | RCV001849321.5 | |
|
SEC23B-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
Apr 8, 2024 | RCV004737239.1 |
| Pathogenic (1) |
criteria provided, single submitter
|
Nov 18, 2023 | RCV002514962.3 |
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
Help
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jan 23, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000203546.7
First in ClinVar: Feb 02, 2015 Last updated: Jun 29, 2015 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Pathogenic
(Mar 05, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital dyserythropoietic anemia, type II
Affected status: yes
Allele origin:
germline
|
DASA
Accession: SCV002107135.2
First in ClinVar: Mar 28, 2022 Last updated: Apr 02, 2022 |
Comment:
The c.1648C>T;p.(Arg550*) variant creates a premature translational stop signal in the SEC23B gene. It is expected to result in an absent or disrupted protein product … (more)
The c.1648C>T;p.(Arg550*) variant creates a premature translational stop signal in the SEC23B gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 20015893; PMID: 22208203) - PS4. The variant is present at low allele frequencies population databases (rs199939108 – gnomAD 0.0005657%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg550*) was detected in trans with a pathogenic variant (PMID: 20015893) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: male
Geographic origin: Brazil
|
|
|
Pathogenic
(May 09, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003825512.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 31, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV005325216.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 31589614, 26522472, 35288346, 22208203, 25044164, 20015893, 30747246, 31839986, 29901818) (less)
|
|
|
Pathogenic
(Nov 09, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital dyserythropoietic anemia, type II
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004223596.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
Variant summary: SEC23B c.1648C>T (p.Arg550X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is … (more)
Variant summary: SEC23B c.1648C>T (p.Arg550X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 5.6e-05 in 251430 control chromosomes. c.1648C>T has been reported in the literature in at-least two individuals affected with Congenital dyserythropoietic anemia, type II, along with two different pathogenic variants in SEC23B (example, Iolascon_2010) . These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 20015893). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Nov 18, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Congenital dyserythropoietic anemia, type II
Cowden syndrome 7
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003258702.2
First in ClinVar: Feb 07, 2023 Last updated: Feb 28, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg550*) in the SEC23B gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg550*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). This variant is present in population databases (rs199939108, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with congenital dyserythropoietic anemia type II (CDAII) (PMID: 20015893). ClinVar contains an entry for this variant (Variation ID: 167668). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Apr 08, 2024)
|
no assertion criteria provided
Method: clinical testing
|
SEC23B-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV005362825.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The SEC23B c.1648C>T variant is predicted to result in premature protein termination (p.Arg550*). This variant has previously been reported to be causative for congenital dyserythropoietic … (more)
The SEC23B c.1648C>T variant is predicted to result in premature protein termination (p.Arg550*). This variant has previously been reported to be causative for congenital dyserythropoietic anemia (Iolascon et al. 2010. PubMed ID: 20015893; Punzo et al. 2011. PubMed ID: 22208203). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in SEC23B are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
Comment:
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 31589614, 26522472, 35288346, 22208203, 25044164, 20015893, 30747246, 31839986, 29901818)
Comment:
Variant summary: SEC23B c.1648C>T (p.Arg550X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 5.6e-05 in 251430 control chromosomes. c.1648C>T has been reported in the literature in at-least two individuals affected with Congenital dyserythropoietic anemia, type II, along with two different pathogenic variants in SEC23B (example, Iolascon_2010) . These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 20015893). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Arg550*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). This variant is present in population databases (rs199939108, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with congenital dyserythropoietic anemia type II (CDAII) (PMID: 20015893). ClinVar contains an entry for this variant (Variation ID: 167668). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The SEC23B c.1648C>T variant is predicted to result in premature protein termination (p.Arg550*). This variant has previously been reported to be causative for congenital dyserythropoietic anemia (Iolascon et al. 2010. PubMed ID: 20015893; Punzo et al. 2011. PubMed ID: 22208203). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in SEC23B are expected to be pathogenic. This variant is interpreted as pathogenic.
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. |
Comment:
The c.1648C>T;p.(Arg550*) variant creates a premature translational stop signal in the SEC23B gene. It is expected to result in an absent or disrupted protein product - PVS1. This sequence change has been observed in affected individual(s) and ClinVar contains an entry for this variant (PMID: 20015893; PMID: 22208203) - PS4. The variant is present at low allele frequencies population databases (rs199939108 – gnomAD 0.0005657%; ABraOM no frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Arg550*) was detected in trans with a pathogenic variant (PMID: 20015893) - PM3. In summary, the currently available evidence indicates that the variant is pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 31589614, 26522472, 35288346, 22208203, 25044164, 20015893, 30747246, 31839986, 29901818)
Comment:
Variant summary: SEC23B c.1648C>T (p.Arg550X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. The variant allele was found at a frequency of 5.6e-05 in 251430 control chromosomes. c.1648C>T has been reported in the literature in at-least two individuals affected with Congenital dyserythropoietic anemia, type II, along with two different pathogenic variants in SEC23B (example, Iolascon_2010) . These data indicate that the variant is very likely associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 20015893). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
This sequence change creates a premature translational stop signal (p.Arg550*) in the SEC23B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SEC23B are known to be pathogenic (PMID: 19561605, 25044164). This variant is present in population databases (rs199939108, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with congenital dyserythropoietic anemia type II (CDAII) (PMID: 20015893). ClinVar contains an entry for this variant (Variation ID: 167668). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The SEC23B c.1648C>T variant is predicted to result in premature protein termination (p.Arg550*). This variant has previously been reported to be causative for congenital dyserythropoietic anemia (Iolascon et al. 2010. PubMed ID: 20015893; Punzo et al. 2011. PubMed ID: 22208203). This variant is reported in 0.015% of alleles in individuals of East Asian descent in gnomAD. Nonsense variants in SEC23B are expected to be pathogenic. This variant is interpreted as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Retrospective cohort study of 205 cases with congenital dyserythropoietic anemia type II: definition of clinical and molecular spectrum and identification of new diagnostic scores. | Russo R | American journal of hematology | 2014 | PMID: 25044164 |
| Congenital dyserythropoietic anemia type II: molecular analysis and expression of the SEC23B gene. | Punzo F | Orphanet journal of rare diseases | 2011 | PMID: 22208203 |
| Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship. | Iolascon A | Haematologica | 2010 | PMID: 20015893 |
| Mutations affecting the secretory COPII coat component SEC23B cause congenital dyserythropoietic anemia type II. | Schwarz K | Nature genetics | 2009 | PMID: 19561605 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=SEC23B | - | - | - | - |
Text-mined citations for rs199939108 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 13, 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.