chr2-28783757-G-GA

Position:

• chr2-28783757-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002709.3(PPP1CB):​c.521-138dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 459,862 control chromosomes in the GnomAD database, including 2,266 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2131 hom., cov: 28)
  • Exomes 𝑓: 0.20 (135 hom.)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.164

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]

SPDYA (HGNC:30613): (speedy/RINGO cell cycle regulator family member A) Enables protein kinase activator activity and protein kinase binding activity. Involved in several processes, including G1/S transition of mitotic cell cycle; positive regulation of cell population proliferation; and positive regulation of protein kinase activity. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-28783757-G-GA is Benign according to our data. Variant chr2-28783757-G-GA is described in ClinVar as [Benign]. Clinvar id is 1221102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB	NM_002709.3	c.521-138dup		intron_variant		ENST00000395366.3
PPP1CB	NM_206876.2	c.521-138dup		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000395366.3	c.521-138dup		intron_variant		1	NM_002709.3	P1

Frequencies

GnomAD3 genomes AF: 0.162 AC: 22849 AN: 140828 Hom.: 2126 Cov.: 28

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0898

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.140

GnomAD4 exome AF: 0.200 AC: 63672 AN: 318988 Hom.: 135 AF XY: 0.202 AC XY: 34202 AN XY: 169720

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.216

Gnomad4 ASJ exome AF: 0.179

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.227

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.187

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.162 AC: 22877 AN: 140874 Hom.: 2131 Cov.: 28 AF XY: 0.164 AC XY: 11170 AN XY: 68040

Gnomad4 AFR AF: 0.276

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.0898

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.147

Gnomad4 FIN AF: 0.162

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.141

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11449670; hg19: chr2-29006623;