chr2-44209312-G-A

Variant names:

• chr2-44209312-G-A
• rs138417279
• NM_002706.6:c.949G>A

Variant summary

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

The NM_002706.6(PPM1B):​c.949G>A​(p.Glu317Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E317Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPM1B NM_002706.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 10.0
• 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 2 ACMG points.

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

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.949G>A	p.Glu317Lys	missense	Exon 3 of 6	NP_002697.1	O75688-1
	PPM1B	NM_177968.4		c.949G>A	p.Glu317Lys	missense	Exon 3 of 6	NP_808907.1	O75688-2
	PPM1B	NM_001033557.3		c.949G>A	p.Glu317Lys	missense	Exon 3 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.949G>A	p.Glu317Lys	missense	Exon 3 of 6	ENSP00000282412.4	O75688-1
	PPM1B	ENST00000378551.6	TSL:1	c.949G>A	p.Glu317Lys	missense	Exon 3 of 6	ENSP00000367813.2	O75688-2
	PPM1B	ENST00000409432.7	TSL:1	c.949G>A	p.Glu317Lys	missense	Exon 3 of 6	ENSP00000387287.3	O75688-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.070	D
BayesDel_noAF	Benign	-0.14
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.55	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		10
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.30
Sift	Benign	0.13	T
Sift4G	Benign	0.38	T
Polyphen		0.35	B
Vest4		0.81
MutPred		0.42		Gain of ubiquitination at E317 (P = 0.009)
MVP		0.68
MPC		0.31
ClinPred		0.96	D
GERP RS		5.2
Varity_R		0.48
gMVP		0.63
Mutation Taster		=16/84	disease causing

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: rs138417279; hg19: chr2-44436451; COSMIC: COSV56767097;