2-44202008-A-G

Variant names:

• chr2-44202008-A-G
• rs766283721
• NM_002706.6:c.809A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002706.6(PPM1B):​c.809A>G​(p.Asn270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPM1B NM_002706.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09649837).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002706.6. 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
	PPM1B	NM_002706.6	MANE Select	c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	NP_002697.1	O75688-1
	PPM1B	NM_177968.4		c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	NP_808907.1	O75688-2
	PPM1B	NM_001033557.3		c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	NP_001028729.1	O75688-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1B	ENST00000282412.9	TSL:1 MANE Select	c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	ENSP00000282412.4	O75688-1
	PPM1B	ENST00000378551.6	TSL:1	c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	ENSP00000367813.2	O75688-2
	PPM1B	ENST00000409432.7	TSL:1	c.809A>G	p.Asn270Ser	missense	Exon 2 of 6	ENSP00000387287.3	O75688-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.76
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.23
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.096	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.3	N
PhyloP100		2.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.097
Sift	Benign	0.61	T
Sift4G	Benign	0.66	T
Polyphen		0.0	B
Vest4		0.067
MutPred		0.44		Gain of disorder (P = 0.0473)
MVP		0.52
MPC		0.11
ClinPred		0.62	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.16
gMVP		0.11
Mutation Taster		=70/30	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs766283721; hg19: chr2-44429147; COSMIC: COSV56766182; COSMIC: COSV56766182;