rs144534508

Variant names:

• chr2-44201251-G-A
• rs144534508
• NM_002706.6:c.52G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_002706.6(PPM1B):​c.52G>A​(p.Ala18Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000229 in 1,613,054 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: PPM1B NM_002706.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.88
• Publications: 3 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008306444).
• BP6: Variant 2-44201251-G-A is Benign according to our data. Variant chr2-44201251-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 785963.Status of the report is criteria_provided_single_submitter, 1 stars.

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.52G>A	p.Ala18Thr	missense	Exon 2 of 6	NP_002697.1	O75688-1
	PPM1B	NM_177968.4		c.52G>A	p.Ala18Thr	missense	Exon 2 of 6	NP_808907.1	O75688-2
	PPM1B	NM_001033557.3		c.52G>A	p.Ala18Thr	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.52G>A	p.Ala18Thr	missense	Exon 2 of 6	ENSP00000282412.4	O75688-1
	PPM1B	ENST00000378551.6	TSL:1	c.52G>A	p.Ala18Thr	missense	Exon 2 of 6	ENSP00000367813.2	O75688-2
	PPM1B	ENST00000409432.7	TSL:1	c.52G>A	p.Ala18Thr	missense	Exon 2 of 6	ENSP00000387287.3	O75688-4

Frequencies

GnomAD3 genomes AF: 0.00126 AC: 192 AN: 152148 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00423

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000294

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000443 AC: 111 AN: 250734 AF XY: 0.000399

Gnomad AFR exome AF: 0.00511

Gnomad AMR exome AF: 0.000638

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000656

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1460788 Hom.: 1 Cov.: 31 AF XY: 0.000109 AC XY: 79 AN XY: 726504

African (AFR) AF: 0.00359 AC: 120 AN: 33462

American (AMR) AF: 0.000717 AC: 32 AN: 44610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111312

Other (OTH) AF: 0.000381 AC: 23 AN: 60350

GnomAD4 genome AF: 0.00126 AC: 192 AN: 152266 Hom.: 0 Cov.: 32 AF XY: 0.00109 AC XY: 81 AN XY: 74454

African (AFR) AF: 0.00421 AC: 175 AN: 41542

American (AMR) AF: 0.000719 AC: 11 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

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

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000463 Hom.: 0

Bravo AF: 0.00144

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000486 AC: 59

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.050
Eigen_PC	Benign	0.21
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0083	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.18	N
PhyloP100		5.9
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.10
Sift	Benign	0.43	T
Sift4G	Benign	0.55	T
Polyphen		0.0010	B
Vest4		0.049
MVP		0.42
MPC		0.14
ClinPred		0.026	T
GERP RS		5.8
PromoterAI		-0.018	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.13
gMVP		0.29
Mutation Taster		=78/22	polymorphism

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: rs144534508; hg19: chr2-44428390;