2-28784117-C-T

Position:

• chr2-28784117-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002709.3(PPP1CB):​c.592+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00524 in 573,856 control chromosomes in the GnomAD database, including 67 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (21 hom.)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.826

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-28784117-C-T is Benign according to our data. Variant chr2-28784117-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1207392.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2144/152290) while in subpopulation AFR AF= 0.048 (1994/41552). AF 95% confidence interval is 0.0462. There are 46 homozygotes in gnomad4. There are 1000 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2144 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1CB	NM_002709.3	c.592+139C>T		intron_variant		ENST00000395366.3
PPP1CB	NM_206876.2	c.592+139C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1CB	ENST00000395366.3	c.592+139C>T		intron_variant		1	NM_002709.3	P1

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2125 AN: 152172 Hom.: 44 Cov.: 32

Gnomad AFR AF: 0.0477

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.00204 AC: 861 AN: 421566 Hom.: 21 AF XY: 0.00177 AC XY: 392 AN XY: 220854

Gnomad4 AFR exome AF: 0.0493

Gnomad4 AMR exome AF: 0.00334

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000228

Gnomad4 FIN exome AF: 0.0000317

Gnomad4 NFE exome AF: 0.000274

Gnomad4 OTH exome AF: 0.00503

GnomAD4 genome AF: 0.0141 AC: 2144 AN: 152290 Hom.: 46 Cov.: 32 AF XY: 0.0134 AC XY: 1000 AN XY: 74478

Gnomad4 AFR AF: 0.0480

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.0117 Hom.: 5

Bravo AF: 0.0157

Asia WGS AF: 0.00780 AC: 28 AN: 3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 17, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.8
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs112229504; hg19: chr2-29006983;