2-28783757-GAAAA-GA

Variant names:

• chr2-28783757-GAAA-G
• rs11449670
• NM_002709.3:c.521-140_521-138delAAA

Variant summary

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

The NM_002709.3(PPP1CB):​c.521-140_521-138delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000838 in 334,178 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 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.000084 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353
• 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.521-140_521-138delAAA		intron_variant	Intron 4 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.521-140_521-138delAAA		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_521-147delAAA		intron_variant	Intron 4 of 7	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141088 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

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: 0.0000838 AC: 28 AN: 334178 Hom.: 0 AF XY: 0.0000562 AC XY: 10 AN XY: 177978

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

African (AFR) AF: 0.000221 AC: 2 AN: 9050

American (AMR) AF: 0.0000691 AC: 1 AN: 14462

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9268

East Asian (EAS) AF: 0.0000453 AC: 1 AN: 22098

South Asian (SAS) AF: 0.0000612 AC: 2 AN: 32658

European-Finnish (FIN) AF: 0.000288 AC: 6 AN: 20816

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1318

European-Non Finnish (NFE) AF: 0.0000630 AC: 13 AN: 206196

Other (OTH) AF: 0.000164 AC: 3 AN: 18312

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 141088 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68098

African (AFR) AF: 0.00 AC: 0 AN: 38674

American (AMR) AF: 0.00 AC: 0 AN: 14036

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: 8084

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64462

Other (OTH) AF: 0.00 AC: 0 AN: 1920

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.35
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs11449670; hg19: chr2-29006623;