NM_002706.6:c.1134+2956G>A

Variant names:

• chr2-44221493-G-A
• rs2053456
• NM_002706.6:c.1134+2956G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002706.6(PPM1B):​c.1134+2956G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 152,134 control chromosomes in the GnomAD database, including 48,799 homozygotes. 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: 𝑓 0.80 (48799 hom., cov: 32)
• Consequence: PPM1B NM_002706.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 2 publications found

Genes affected

PPM1B (HGNC:9276): (protein phosphatase, Mg2+/Mn2+ dependent 1B) The protein encoded by this gene is a member of the PP2C family of Ser/Thr protein phosphatases. PP2C family members are known to be negative regulators of cell stress response pathways. This phosphatase has been shown to dephosphorylate cyclin-dependent kinases (CDKs), and thus may be involved in cell cycle control. Overexpression of this phosphatase is reported to cause cell-growth arrest or cell death. Alternative splicing results in multiple transcript variants encoding different isoforms. Additional transcript variants have been described, but currently do not represent full-length sequences. [provided by RefSeq, Jul 2008]

ENSG00000285542 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.868 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1B	NM_002706.6	c.1134+2956G>A		intron_variant	Intron 5 of 5	ENST00000282412.9	NP_002697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1B	ENST00000282412.9	c.1134+2956G>A		intron_variant	Intron 5 of 5	1	NM_002706.6	ENSP00000282412.4
ENSG00000285542	ENST00000649044.1	n.1134+2956G>A		intron_variant	Intron 5 of 14			ENSP00000497083.1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121563 AN: 152016 Hom.: 48760 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.737

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.667

Gnomad SAS AF: 0.890

Gnomad FIN AF: 0.738

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.824

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.800 AC: 121662 AN: 152134 Hom.: 48799 Cov.: 32 AF XY: 0.797 AC XY: 59235 AN XY: 74366

African (AFR) AF: 0.819 AC: 33985 AN: 41490

American (AMR) AF: 0.811 AC: 12392 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2952 AN: 3472

East Asian (EAS) AF: 0.667 AC: 3454 AN: 5178

South Asian (SAS) AF: 0.890 AC: 4293 AN: 4822

European-Finnish (FIN) AF: 0.738 AC: 7797 AN: 10568

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54132 AN: 68008

Other (OTH) AF: 0.826 AC: 1742 AN: 2110

Alfa AF: 0.804 Hom.: 78451

Bravo AF: 0.802

Asia WGS AF: 0.796 AC: 2767 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		0.21
Mutation Taster		=100/0	polymorphism (auto)

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: rs2053456; hg19: chr2-44448632;