This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.632A>C (p.Gln211Pro) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. It localizes to the B56δ regulatory subunit in the PPP2R5D protein in close proximity to other previously reported Pathogenic variants (PMID: 26168268). Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.632A>C (p.Gln211Pro) variant is classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_006245.4(PPP2R5D):c.632A>C (p.Gln211Pro)
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.
(6)
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.
Conflicting classifications of pathogenicity
Pathogenic(2); Likely pathogenic(2); Uncertain significance(1)
Pathogenic(2); Likely pathogenic(2); Uncertain significance(1)
6
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_006245.4(PPP2R5D):c.632A>C (p.Gln211Pro)
Variation ID: 982374 Accession: VCV000982374.5
- Type and length
-
single nucleotide variant, 1 bp
- Location
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Cytogenetic: 6p21.1 6: 43007305 (GRCh38) [ NCBI UCSC ] 6: 42975043 (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 Oct 30, 2020 Jun 2, 2024 Sep 20, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006245.4:c.632A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_006236.1:p.Gln211Pro missense NM_001270476.2:c.179A>C NP_001257405.1:p.Gln60Pro missense NM_180976.3:c.536A>C NP_851307.1:p.Gln179Pro missense NM_180977.3:c.314A>C NP_851308.1:p.Gln105Pro missense NC_000006.12:g.43007305A>C NC_000006.11:g.42975043A>C NG_050636.1:g.27807A>C - Protein change
- Q105P, Q179P, Q211P, Q60P
- Other names
- -
- Canonical SPDI
- NC_000006.12:43007304:A: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.
- -
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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. |
|||
| PPP2R5D | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
476 | 531 | |
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/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Sep 20, 2023 | RCV001261947.5 | |
| Uncertain significance (1) |
criteria provided, single submitter
|
Jan 15, 2023 | RCV003679050.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Jun 10, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hogue-Janssens syndrome 1
Affected status: yes
Allele origin:
de novo
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV001439298.1
First in ClinVar: Oct 30, 2020 Last updated: Oct 30, 2020 |
|
|
|
Pathogenic
(Jul 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
MENTAL RETARDATION, AUTOSOMAL DOMINANT 35
Affected status: yes
Allele origin:
germline
|
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego
Accession: SCV001445890.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population … (more)
This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.632A>C (p.Gln211Pro) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. It localizes to the B56δ regulatory subunit in the PPP2R5D protein in close proximity to other previously reported Pathogenic variants (PMID: 26168268). Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.632A>C (p.Gln211Pro) variant is classified as Pathogenic. (less)
|
|
|
Likely pathogenic
(Feb 05, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Hogue-Janssens syndrome 1
Affected status: yes
Allele origin:
de novo
|
Baylor Genetics
Accession: SCV001521017.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
|
|
|
Uncertain significance
(Jan 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV004424545.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
Comment:
ClinVar contains an entry for this variant (Variation ID: 982374). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. … (more)
ClinVar contains an entry for this variant (Variation ID: 982374). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 211 of the PPP2R5D protein (p.Gln211Pro). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
|
|
|
Pathogenic
(Sep 20, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hogue-Janssens syndrome 1
Affected status: yes
Allele origin:
unknown
|
Center for Molecular Medicine, Children’s Hospital of Fudan University
Accession: SCV005046473.1
First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024 |
|
|
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Pathogenic
(Aug 13, 2018)
|
no assertion criteria provided
Method: provider interpretation
|
Hogue-Janssens syndrome 1
Affected status: yes
Allele origin:
de novo
|
GenomeConnect - Simons Searchlight
Accession: SCV001443621.1
First in ClinVar: Nov 21, 2020 Last updated: Nov 21, 2020 |
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-13 and interpreted as Pathogenic. The reporting laboratory … (more)
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-13 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight. (less)
Observation 1:
Number of individuals with the variant: 1
Clinical Features:
Caesarian section (present) , Neonatal hypotonia (present) , Feeding difficulties in infancy (present) , Generalized hypotonia (present) , Macrocephalus (present) , Seizures (present) , Focal … (more)
Caesarian section (present) , Neonatal hypotonia (present) , Feeding difficulties in infancy (present) , Generalized hypotonia (present) , Macrocephalus (present) , Seizures (present) , Focal seizures without impairment of consciousness or awareness (present) (less)
Age: 0-9 years
Sex: male
Testing laboratory: East of England Genomics Medicine Centre
Date variant was reported to submitter: 2018-04-27
Testing laboratory interpretation: Pathogenic
Observation 2:
Number of individuals with the variant: 1
Clinical Features:
Premature birth (present) , Neonatal seizure (present) , Neonatal hypotonia (present) , Feeding difficulties in infancy (present) , Generalized hypotonia (present) , Microcephaly (present) , … (more)
Premature birth (present) , Neonatal seizure (present) , Neonatal hypotonia (present) , Feeding difficulties in infancy (present) , Generalized hypotonia (present) , Microcephaly (present) , Cerebral palsy (present) , Seizures (present) , Generalized tonic-clonic seizures (present) , Absence seizures (present) , Constipation (present) , Failure to thrive (present) , Short stature (present) , Abnormality of the skin (present) , Eczema (present) (less)
Age: 0-9 years
Sex: male
Testing laboratory: Karolinska University Laboratory
Date variant was reported to submitter: 2016-03-14
Testing laboratory interpretation: Pathogenic
|
Comment:
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
ClinVar contains an entry for this variant (Variation ID: 982374). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 211 of the PPP2R5D protein (p.Gln211Pro). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-13 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
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:
This variant has not been previously reported or functionally characterized in the literature to our knowledge. It is absent from the ExAC and gnomAD population databases and thus is presumed to be rare. The c.632A>C (p.Gln211Pro) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. It localizes to the B56δ regulatory subunit in the PPP2R5D protein in close proximity to other previously reported Pathogenic variants (PMID: 26168268). Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.632A>C (p.Gln211Pro) variant is classified as Pathogenic.
Comment:
This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Comment:
ClinVar contains an entry for this variant (Variation ID: 982374). This variant has not been reported in the literature in individuals affected with PPP2R5D-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 211 of the PPP2R5D protein (p.Gln211Pro). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Comment:
Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-08-13 and interpreted as Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs1762136390 ...
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 Sep 29, 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.