2-28783757-GAAAA-GAAAAAAAA

Variant names:

• chr2-28783757-G-GAAAA
• rs11449670
• NM_002709.3:c.521-141_521-138dupAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002709.3(PPP1CB):​c.521-141_521-138dupAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000299 in 334,434 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000030 (0 hom.)
  • Failed GnomAD Quality Control
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002709.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	NM_002709.3	MANE Select	c.521-141_521-138dupAAAA		intron	N/A	NP_002700.1	P62140
	PPP1CB	NM_206876.2		c.521-141_521-138dupAAAA		intron	N/A	NP_996759.1	P62140

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1CB	ENST00000395366.3	TSL:1 MANE Select	c.521-150_521-149insAAAA		intron	N/A	ENSP00000378769.2	P62140
	PPP1CB	ENST00000296122.10	TSL:1	c.521-150_521-149insAAAA		intron	N/A	ENSP00000296122.6	P62140
	PPP1CB	ENST00000703174.1		c.644-150_644-149insAAAA		intron	N/A	ENSP00000515220.1	A0A8V8TRH9

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 141090 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: 0.00000299 AC: 1 AN: 334434 Hom.: 0 AF XY: 0.00000561 AC XY: 1 AN XY: 178122

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

African (AFR) AF: 0.00 AC: 0 AN: 9054

American (AMR) AF: 0.00 AC: 0 AN: 14478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9276

East Asian (EAS) AF: 0.00 AC: 0 AN: 22112

South Asian (SAS) AF: 0.0000306 AC: 1 AN: 32686

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20828

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1322

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 206348

Other (OTH) AF: 0.00 AC: 0 AN: 18330

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 141090 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 68096

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: 64464

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;