2-28752130-G-A

Variant names:

• chr2-28752130-G-A
• rs367543172
• NM_002709.3:c.6G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_002709.3(PPP1CB):​c.6G>A​(p.Ala2Ala) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000215 in 1,397,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PPP1CB NM_002709.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 O:1
• Conservation: PhyloP100: 4.16
• Publications: 1 publications found

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

PPP1CB Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 2-28752130-G-A is Benign according to our data. Variant chr2-28752130-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 98363.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.6G>A	p.Ala2Ala	synonymous_variant	Exon 1 of 8	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.6G>A	p.Ala2Ala	synonymous_variant	Exon 2 of 9		NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.6G>A	p.Ala2Ala	synonymous_variant	Exon 1 of 8	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1397500 Hom.: 0 Cov.: 31 AF XY: 0.00000290 AC XY: 2 AN XY: 689322

African (AFR) AF: 0.00 AC: 0 AN: 31276

American (AMR) AF: 0.00 AC: 0 AN: 35652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25132

East Asian (EAS) AF: 0.00 AC: 0 AN: 35458

South Asian (SAS) AF: 0.00 AC: 0 AN: 79224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49018

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1078120

Other (OTH) AF: 0.00 AC: 0 AN: 57928

GnomAD4 genome Cov.: 30

ClinVar

Significance: Likely benign

Submissions summary: Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1 Other:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Psychiatry Genetics Yale University

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	15
DANN	Benign	0.97
PhyloP100		4.2
PromoterAI		-0.66	Under-expression
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs367543172; hg19: chr2-28974996;