NM_002709.3:c.521-139_521-138delAA

Variant names:

• chr2-28783757-GAA-G
• rs11449670
• NM_002709.3:c.521-139_521-138delAA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002709.3(PPP1CB):​c.521-139_521-138delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 470,642 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000071 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0023 (0 hom.)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.320
• 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.521-139_521-138delAA		intron_variant	Intron 4 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.521-139_521-138delAA		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.521-149_521-148delAA		intron_variant	Intron 4 of 7	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.00000709 AC: 1 AN: 141074 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000259

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00231 AC: 760 AN: 329568 Hom.: 0 AF XY: 0.00240 AC XY: 421 AN XY: 175482

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

African (AFR) AF: 0.00145 AC: 13 AN: 8952

American (AMR) AF: 0.00253 AC: 36 AN: 14238

Ashkenazi Jewish (ASJ) AF: 0.00185 AC: 17 AN: 9168

East Asian (EAS) AF: 0.00197 AC: 43 AN: 21820

South Asian (SAS) AF: 0.00168 AC: 54 AN: 32144

European-Finnish (FIN) AF: 0.00224 AC: 46 AN: 20534

Middle Eastern (MID) AF: 0.00153 AC: 2 AN: 1308

European-Non Finnish (NFE) AF: 0.00248 AC: 505 AN: 203326

Other (OTH) AF: 0.00243 AC: 44 AN: 18078

⚠️ 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: 0.00000709 AC: 1 AN: 141074 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68088

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

African (AFR) AF: 0.0000259 AC: 1 AN: 38674

American (AMR) AF: 0.00 AC: 0 AN: 14034

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3318

East Asian (EAS) AF: 0.00 AC: 0 AN: 4876

South Asian (SAS) AF: 0.00 AC: 0 AN: 4540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64456

Other (OTH) AF: 0.00 AC: 0 AN: 1918

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.32
Mutation Taster		=100/0	polymorphism

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;