2-28783757-GAAAA-GAAAAAAA

Variant names:

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

Variant summary

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

The NM_002709.3(PPP1CB):​c.521-140_521-138dupAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000799 in 475,416 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: 0.00011 (0 hom.)
• Consequence: PPP1CB NM_002709.3 intron
• Clinical Significance: Not reported in ClinVar
• 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: 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_521-138dupAAA		intron_variant	Intron 4 of 7	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.521-140_521-138dupAAA		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_521-149insAAA		intron_variant	Intron 4 of 7	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes AF: 0.00000709 AC: 1 AN: 141092 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: 0.000124

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 37 AN: 334324 Hom.: 0 AF XY: 0.000118 AC XY: 21 AN XY: 178052

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

African (AFR) AF: 0.000332 AC: 3 AN: 9048

American (AMR) AF: 0.000207 AC: 3 AN: 14474

Ashkenazi Jewish (ASJ) AF: 0.000108 AC: 1 AN: 9274

East Asian (EAS) AF: 0.00 AC: 0 AN: 22100

South Asian (SAS) AF: 0.000153 AC: 5 AN: 32670

European-Finnish (FIN) AF: 0.000192 AC: 4 AN: 20820

Middle Eastern (MID) AF: 0.000756 AC: 1 AN: 1322

European-Non Finnish (NFE) AF: 0.0000921 AC: 19 AN: 206298

Other (OTH) AF: 0.0000546 AC: 1 AN: 18318

⚠️ 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: 141092 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68098

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

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: 0.000124 AC: 1 AN: 8086

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64464

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

⚠️ 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.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11449670; hg19: chr2-29006623;