2-28784096-C-T

Variant names:

• chr2-28784096-C-T
• rs114802424
• NM_002709.3:c.592+118C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002709.3(PPP1CB):​c.592+118C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 677,784 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.018 (40 hom., cov: 32)
  • Exomes 𝑓: 0.023 (179 hom.)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.442

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 2-28784096-C-T is Benign according to our data. Variant chr2-28784096-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1211536.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0175 (2668/152226) while in subpopulation NFE AF = 0.0274 (1864/67998). AF 95% confidence interval is 0.0264. There are 40 homozygotes in GnomAd4. There are 1201 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.
• BS2: High AC in GnomAd4 at 2668 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.592+118C>T		intron_variant	Intron 5 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.592+118C>T		intron_variant	Intron 6 of 8		NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.592+118C>T		intron_variant	Intron 5 of 7	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2668 AN: 152108 Hom.: 40 Cov.: 32

Gnomad AFR AF: 0.00471

Gnomad AMI AF: 0.0800

Gnomad AMR AF: 0.00622

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0227

Gnomad FIN AF: 0.0182

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0274

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0233 AC: 12220 AN: 525558 Hom.: 179 AF XY: 0.0233 AC XY: 6424 AN XY: 275842

Gnomad4 AFR exome AF: 0.00335 AC: 47 AN: 14010

Gnomad4 AMR exome AF: 0.00853 AC: 177 AN: 20746

Gnomad4 ASJ exome AF: 0.0317 AC: 453 AN: 14286

Gnomad4 EAS exome AF: 0.0000955 AC: 3 AN: 31408

Gnomad4 SAS exome AF: 0.0254 AC: 1015 AN: 39992

Gnomad4 FIN exome AF: 0.0186 AC: 694 AN: 37226

Gnomad4 NFE exome AF: 0.0274 AC: 9245 AN: 337764

Gnomad4 Remaining exome AF: 0.0206 AC: 566 AN: 27486

GnomAD4 genome AF: 0.0175 AC: 2668 AN: 152226 Hom.: 40 Cov.: 32 AF XY: 0.0161 AC XY: 1201 AN XY: 74436

Gnomad4 AFR AF: 0.00469 AC: 0.00469427 AN: 0.00469427

Gnomad4 AMR AF: 0.00621 AC: 0.00621077 AN: 0.00621077

Gnomad4 ASJ AF: 0.0300 AC: 0.0299539 AN: 0.0299539

Gnomad4 EAS AF: 0.000578 AC: 0.000577812 AN: 0.000577812

Gnomad4 SAS AF: 0.0226 AC: 0.0225579 AN: 0.0225579

Gnomad4 FIN AF: 0.0182 AC: 0.0181509 AN: 0.0181509

Gnomad4 NFE AF: 0.0274 AC: 0.0274126 AN: 0.0274126

Gnomad4 OTH AF: 0.0137 AC: 0.0137311 AN: 0.0137311

Alfa AF: 0.00743 Hom.: 2

Bravo AF: 0.0161

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 24, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.44
DANN	Benign	0.50
Mutation Taster		=99/1	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

Publications

LitVar

Other links and lift over

dbSNP: rs114802424; hg19: chr2-29006962;