chr2-28751725-C-T

Variant names:

• chr2-28751725-C-T
• rs115360250
• ENST00000757369.1:n.52G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000757369.1(PPP1CB-DT):​n.52G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000324 in 92,530 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000032 (0 hom.)
• Consequence: PPP1CB-DT ENST00000757369.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 0 publications found

Genes affected

PPP1CB-DT (HGNC:55829): (PPP1CB divergent transcript)

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]

PPP1CB Gene-Disease associations (from GenCC):

• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome-like disorder with loose anagen hair 2

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.-400C>T		upstream_gene_variant		ENST00000395366.3	NP_002700.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.-400C>T		upstream_gene_variant		1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.0000324 AC: 3 AN: 92530 Hom.: 0 Cov.: 0 AF XY: 0.0000186 AC XY: 1 AN XY: 53760

⚠️ 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: 882

American (AMR) AF: 0.00 AC: 0 AN: 732

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1942

East Asian (EAS) AF: 0.000693 AC: 1 AN: 1442

South Asian (SAS) AF: 0.00 AC: 0 AN: 20542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 328

European-Non Finnish (NFE) AF: 0.0000353 AC: 2 AN: 56672

Other (OTH) AF: 0.00 AC: 0 AN: 4582

⚠️ 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 Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.1
DANN	Benign	0.93
PhyloP100		-1.1
PromoterAI		-0.038	Neutral

Splicing

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

Other links and lift over

dbSNP: rs115360250; hg19: chr2-28974591;