VCV000747303.18 - ClinVar

NM_002709.3(PPP1CB):c.53-9G>A

Germline

Reviewed by expert panel

Reviewed by expert panel. Learn more about how ClinVar calculates review status.

Benign

for RASopathy

Classification is based on the expert panel submission

Dec 2024 by ClinGen RASopathy Variant Curation Expert Panel

The classification is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

FDA Recognized Database

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002709.3(PPP1CB):c.53-9G>A

Variation ID: 747303 Accession: VCV000747303.18

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2p23.2 2: 28776842 (GRCh38) [ NCBI UCSC ] 2: 28999708 (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	Dec 17, 2019	Mar 7, 2026	Dec 3, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_002709.3:c.53-9G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		intron variant
NM_206876.2:c.53-9G>A		intron variant
NC_000002.12:g.28776842G>A
NC_000002.11:g.28999708G>A
NG_052878.1:g.30095G>A

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000002.12:28776841:G:A

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.

0.00100 (A)

Allele frequency Help The frequency of the allele represented by this VCV record.

Trans-Omics for Precision Medicine (TOPMed) 0.00180

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00223

The Genome Aggregation Database (gnomAD), exomes 0.00047

Exome Aggregation Consortium (ExAC) 0.00055

1000 Genomes Project 30x 0.00094

1000 Genomes Project 0.00100

The Genome Aggregation Database (gnomAD) 0.00172

Links

ClinGen: CA1589161 dbSNP: rs368197884 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.
PPP1CB		No evidence available	No evidence available	GRCh38 GRCh37	371	406

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.
not provided	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 31, 2026	RCV000924000.13
Noonan syndrome-like disorder with loose anagen hair 2	Likely benign (1)	criteria provided, single submitter	May 24, 2022	RCV002495548.1
PPP1CB-related disorder	Benign (1)	no assertion criteria provided	Oct 28, 2019	RCV003970517.2
not specified	Benign (1)	criteria provided, single submitter	Dec 27, 2024	RCV005236443.1
RASopathy	Benign (1)	reviewed by expert panel	Dec 3, 2024	RCV005253658.1

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.	Expand all rows Collapse all rows 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 (Dec 03, 2024) C Contributing to aggregate classification	reviewed by expert panel (ClinGen RASopathy ACMG Specifications PPP1CB V1.3.0)	RASopathy (Autosomal dominant inheritance)	ClinGen RASopathy Variant Curation Expert Panel FDA Recognized Database Accession: SCV005903440.1 First in ClinVar: Apr 13, 2025 Last updated: Apr 13, 2025	Other databases https://erepo.clinicalgenome.org… https://erepo.clinicalgenome.org/evrepo/ui/interpretation/0c73b719-a9d3-4ddf-ad9f-d72869456e33 Comment: show The c.53-9G>A variant in PPP1CB is an intronic splicing variant located in intron 1 of PPP1CB. The filtering allele frequency in gnomAD v2 is 0.5284% in the African American population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1. (RASopathy VCEP specifications version 1.3; 12/3/2024) (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: unknown Observation 1 Collection method: curation Allele origin: germline Affected status: unknown

Likely benign (Sep 24, 2019) N Not contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001815362.1 First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (May 24, 2022) N Not contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Noonan syndrome-like disorder with loose anagen hair 2	Fulgent Genetics, Fulgent Genetics Accession: SCV002803513.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Benign (Dec 27, 2024) N Not contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005883774.1 First in ClinVar: Mar 16, 2025 Last updated: Mar 16, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Jan 31, 2026) N Not contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001069501.7 First in ClinVar: Dec 17, 2019 Last updated: Mar 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Oct 28, 2019) N Not contributing to aggregate classification	no assertion criteria provided	PPP1CB-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004781991.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The c.53-9G>A variant in PPP1CB is an intronic splicing variant located in intron 1 of PPP1CB. The filtering allele frequency in gnomAD v2 is 0.5284% in the African American population, which is higher than the ClinGen RASopathy VCEP threshold (>0.0005) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as benign for autosomal dominant RASopathy based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy VCEP: BA1. (RASopathy VCEP specifications version 1.3; 12/3/2024)

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/0c73b719-a9d3-4ddf-ad9f-d72869456e33	-	-	-	-

Text-mined citations for rs368197884 ...

These 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 Mar 08, 2026