2-28783757-GAAAA-GAAAAA

Variant names:

• chr2-28783757-G-GA
• rs11449670
• NM_002709.3:c.521-138dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_002709.3(PPP1CB):​c.521-138dupA 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
• Publications: 0 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]

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 -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 rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.521-138dupA		intron_variant	Intron 4 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.521-138dupA		intron_variant	Intron 5 of 8		NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.521-150_521-149insA		intron_variant	Intron 4 of 7	1	NM_002709.3	ENSP00000378769.2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.290 AC: 2524 AN: 8716

American (AMR) AF: 0.216 AC: 2927 AN: 13560

Ashkenazi Jewish (ASJ) AF: 0.179 AC: 1582 AN: 8816

East Asian (EAS) AF: 0.232 AC: 4870 AN: 21036

South Asian (SAS) AF: 0.227 AC: 7046 AN: 31026

European-Finnish (FIN) AF: 0.207 AC: 4158 AN: 20048

Middle Eastern (MID) AF: 0.194 AC: 247 AN: 1272

European-Non Finnish (NFE) AF: 0.187 AC: 36868 AN: 196998

Other (OTH) AF: 0.197 AC: 3450 AN: 17516

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.276 AC: 10664 AN: 38698

American (AMR) AF: 0.129 AC: 1811 AN: 14026

Ashkenazi Jewish (ASJ) AF: 0.0898 AC: 298 AN: 3318

East Asian (EAS) AF: 0.169 AC: 820 AN: 4860

South Asian (SAS) AF: 0.147 AC: 662 AN: 4514

European-Finnish (FIN) AF: 0.162 AC: 1307 AN: 8046

Middle Eastern (MID) AF: 0.143 AC: 39 AN: 272

European-Non Finnish (NFE) AF: 0.105 AC: 6769 AN: 64328

Other (OTH) AF: 0.141 AC: 272 AN: 1928

Alfa AF: 0.0274 Hom.: 17

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 12, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11449670; hg19: chr2-29006623;