VCV002498148.2 - ClinVar

NM_014225.6(PPP2R1A):c.96C>G (p.Ile32Met)

Germline

Classification

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.

(2)

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.

Likely pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_014225.6(PPP2R1A):c.96C>G (p.Ile32Met)

Variation ID: 2498148 Accession: VCV002498148.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 19q13.41 19: 52201961 (GRCh38) [ NCBI UCSC ] 19: 52705214 (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 15, 2023	Jun 17, 2023	Nov 7, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_014225.6:c.96C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_055040.2:p.Ile32Met	missense
NM_001363656.2:c.-442C>G		5 prime UTR
NR_033500.2:n.141C>G		non-coding transcript variant
NC_000019.10:g.52201961C>G
NC_000019.9:g.52705214C>G
NG_047068.1:g.17160C>G
NG_047068.2:g.16911C>G

... more HGVS ... less HGVS

Protein change

I32M

Other names

Canonical SPDI

NC_000019.10:52201960:C:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

Links

VarSome

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
Gene	OMIM	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.
PPP2R1A		No evidence available	No evidence available	GRCh38 GRCh37	436	486

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.
Houge-Janssens syndrome 2	Likely pathogenic (2)	no assertion criteria provided	Nov 7, 2022	RCV003219209.3

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.
Likely pathogenic (Nov 07, 2022)	no assertion criteria provided Method: clinical testing	Houge-Janssens syndrome 2 Affected status: yes Allele origin: de novo	Undiagnosed Diseases Network, NIH Accession: SCV003915635.1 First in ClinVar: Apr 15, 2023 Last updated: Apr 15, 2023	Number of individuals with the variant: 1 Clinical Features: Oligohydramnios (present) , Hydronephrosis (present) , Microcephaly (present) , Macrotia (present) , Autistic behavior (present) , Eczematoid dermatitis (present) , Short foot (present) , Gliosis … (more) Oligohydramnios (present) , Hydronephrosis (present) , Microcephaly (present) , Macrotia (present) , Autistic behavior (present) , Eczematoid dermatitis (present) , Short foot (present) , Gliosis (present) , Abnormal cerebral white matter morphology (present) , EEG with generalized slow activity (present) , Intellectual disability, severe (present) , Moderate expressive language delay (present) , Moderate receptive language delay (present) , Decreased CSF 5-methyltetrahydrofolate concentration (present) , Chronic constipation (present) , Reduced brain N-acetyl aspartate level by MRS (present) , Short palpebral fissure (present) , Punctate periventricular T2 hyperintense foci (present) , Self-injurious behavior (present) , Flat sella turcica (present) (less) Age: 10-19 years Sex: female Tissue: Blood
not provided (-)	no classification provided Method: phenotyping only	Houge-Janssens syndrome 2 Affected status: yes Allele origin: de novo	GenomeConnect - Brain Gene Registry Accession: SCV003931169.1 First in ClinVar: Jun 17, 2023 Last updated: Jun 17, 2023	Comment: Variant classified as Likely pathogenic and reported on 11-07-2017 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect … (more) Variant classified as Likely pathogenic and reported on 11-07-2017 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/. (less) Clinical Features: Autistic behavior (present) , Intellectual disability (present) , Ketotic hypoglycemia (present) , Joint hypermobility (present) , Migraine (present) , Abnormal facial shape (present) , Family … (more) Autistic behavior (present) , Intellectual disability (present) , Ketotic hypoglycemia (present) , Joint hypermobility (present) , Migraine (present) , Abnormal facial shape (present) , Family history (present) (less) Indication for testing: Diagnostic Age: 0-9 years Sex: female Method: Exome Sequencing Testing laboratory: GeneDx Date variant was reported to submitter: 2017-11-07 Testing laboratory interpretation: Likely pathogenic

Comment:

Variant classified as Likely pathogenic and reported on 11-07-2017 by GeneDx. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.

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:

Citations for germline classification of this variant

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 this variant ...

Record last updated Jun 23, 2024

ClinVar Genomic variation as it relates to human health

NM_014225.6(PPP2R1A):c.96C>G (p.Ile32Met)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for this variant ...