The NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant has an allele frequency of 0.19422 in the East Asian population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, this variant is present 1394 adult homozygous individuals in gnomADv2.1.1 (distributed in all gnomAD populations)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
ClinVar Genomic variation as it relates to human health
NM_001033855.3(DCLRE1C):c.512C>G (p.Pro171Arg)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001033855.3(DCLRE1C):c.512C>G (p.Pro171Arg)
Variation ID: 35999 Accession: VCV000035999.34
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 10p13 10: 14934728 (GRCh38) [ NCBI UCSC ] 10: 14976727 (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 Apr 4, 2013 Sep 29, 2024 Nov 14, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001033855.3:c.512C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001029027.1:p.Pro171Arg missense NM_001033857.3:c.152C>G NP_001029029.1:p.Pro51Arg missense NM_001033858.3:c.152C>G NP_001029030.1:p.Pro51Arg missense NM_001289076.2:c.167C>G NP_001276005.1:p.Pro56Arg missense NM_001289077.2:c.152C>G NP_001276006.1:p.Pro51Arg missense NM_001289078.2:c.167C>G NP_001276007.1:p.Pro56Arg missense NM_001289079.2:c.152C>G NP_001276008.1:p.Pro51Arg missense NM_001350965.2:c.512C>G NP_001337894.1:p.Pro171Arg missense NM_001350966.2:c.167C>G NP_001337895.1:p.Pro56Arg missense NM_001350967.2:c.152C>G NP_001337896.1:p.Pro51Arg missense NM_022487.4:c.167C>G NP_071932.2:p.Pro56Arg missense NR_110297.2:n.810C>G non-coding transcript variant NR_146960.1:n.934C>G non-coding transcript variant NR_146961.2:n.627C>G non-coding transcript variant NR_146962.1:n.934C>G non-coding transcript variant NC_000010.11:g.14934728G>C NC_000010.10:g.14976727G>C NG_007276.1:g.24368C>G LRG_54:g.24368C>G LRG_54t1:c.512C>G - Protein change
- P171R, P51R, P56R
- Other names
-
NM_001033855.3(DCLRE1C):c.512C>G
- Canonical SPDI
- NC_000010.11:14934727:G:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.11681 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.09032
Exome Aggregation Consortium (ExAC) 0.09054
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.09119
The Genome Aggregation Database (gnomAD) 0.09351
Trans-Omics for Precision Medicine (TOPMed) 0.10427
1000 Genomes Project 0.11681
1000 Genomes Project 30x 0.11711
- 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. |
|||
| DCLRE1C | - | - |
GRCh38 GRCh37 |
1056 | 1105 | |
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. |
|---|---|---|---|---|
| Benign (1) |
criteria provided, single submitter
|
Aug 18, 2011 | RCV000029657.10 | |
| Benign (1) |
criteria provided, single submitter
|
- | RCV000244893.15 | |
| Benign (2) |
criteria provided, single submitter
|
Mar 6, 2018 | RCV000305875.14 | |
| Benign (5) |
reviewed by expert panel
|
Nov 14, 2023 | RCV000988331.21 | |
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Nov 29, 2023 | RCV001650846.19 | |
| Benign (1) |
criteria provided, single submitter
|
Mar 31, 2022 | RCV002496450.8 |
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. |
|
|---|---|---|---|---|---|
|
Benign
(Nov 14, 2023)
|
reviewed by expert panel
Method: curation
|
Severe combined immunodeficiency due to DCLRE1C deficiency
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
FDA Recognized Database
Accession: SCV004102781.1 First in ClinVar: Nov 20, 2023 Last updated: Nov 20, 2023 |
Comment:
The NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant … (more)
The NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant has an allele frequency of 0.19422 in the East Asian population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, this variant is present 1394 adult homozygous individuals in gnomADv2.1.1 (distributed in all gnomAD populations)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting, as specified by the ClinGen SCID VCEP (VCEP specifications version 1). (less)
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000305989.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
|
|
Benign
(Mar 03, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001863142.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 25917813, 21664875, 23701501, 20674517)
|
|
|
benign
(Aug 18, 2011)
|
criteria provided, single submitter
Method: curation, clinical testing
|
SCID
(autosomal unknown)
Affected status: yes, unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000052309.2
First in ClinVar: Apr 04, 2013 Last updated: Mar 28, 2022 |
Comment:
Converted during submission to Benign.
Observation 1:
Tissue: Blood
Observation 2:
Tissue: Blood
Observation 3:
Tissue: Blood
Observation 4:
Tissue: Blood
Observation 5:
Tissue: Blood
Observation 6:
Tissue: Blood
Observation 7:
Tissue: Blood
Observation 8:
Tissue: Blood
Observation 9:
Tissue: Blood
Observation 10:
Tissue: Blood
Observation 11:
Tissue: Blood
Observation 12:
Tissue: Blood
Observation 13:
Tissue: Blood
Observation 14:
Tissue: Blood
Observation 15:
Tissue: Blood
Observation 16:
Tissue: Blood
Observation 17:
Tissue: Blood
Observation 18:
Tissue: Blood
Observation 19:
Tissue: Blood
Observation 20:
Tissue: Blood
Observation 21:
Tissue: Blood
Observation 22:
Tissue: Blood
Observation 23:
Tissue: Blood
Observation 24:
Tissue: Blood
Observation 25:
Tissue: Blood
Observation 26:
Tissue: Blood
Observation 27:
Tissue: Blood
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency due to DCLRE1C deficiency
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001720361.4
First in ClinVar: Jun 15, 2021 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Histiocytic medullary reticulosis
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000361560.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Benign
(Mar 26, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency due to DCLRE1C deficiency
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004806863.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
|
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency due to DCLRE1C deficiency
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138003.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Benign
(Jul 01, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency due to DCLRE1C deficiency
Affected status: no
Allele origin:
germline
|
Genome-Nilou Lab
Accession: SCV001750448.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
Sex: mixed
|
|
|
Benign
(Mar 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Severe combined immunodeficiency due to DCLRE1C deficiency
Histiocytic medullary reticulosis
Affected status: unknown
Allele origin:
unknown
|
Fulgent Genetics, Fulgent Genetics
Accession: SCV002813063.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Nov 29, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000603291.7
First in ClinVar: Oct 02, 2016 Last updated: Feb 20, 2024 |
|
|
|
Benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005316849.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Sep 16, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Omenn syndrome
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001455087.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
|
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Comment:
Comment:
This variant is associated with the following publications: (PMID: 25917813, 21664875, 23701501, 20674517)
Comment:
Converted during submission to Benign.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
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 NM_001033855.3:c.512C>G variant in DCLRE1C is a missense variant predicted to cause the substitution of proline by arginine at amino acid 171 (p.Pro171Arg). This variant has an allele frequency of 0.19422 in the East Asian population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, this variant is present 1394 adult homozygous individuals in gnomADv2.1.1 (distributed in all gnomAD populations)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
Comment:
This variant is associated with the following publications: (PMID: 25917813, 21664875, 23701501, 20674517)
Comment:
Converted during submission to Benign.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| https://erepo.clinicalgenome.org/evrepo/ui/interpretation/b82ebffe-f888-4104-91bf-516686f3b479 | - | - | - | - |
Text-mined citations for rs35441642 ...
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 Nov 25, 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.