2-44201767-C-G

Variant names:

• chr2-44201767-C-G
• NM_002706.6:c.568C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002706.6(PPM1B):​c.568C>G​(p.Gln190Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 7.91

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1B	NM_002706.6	c.568C>G	p.Gln190Glu	missense_variant	Exon 2 of 6	ENST00000282412.9	NP_002697.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1B	ENST00000282412.9	c.568C>G	p.Gln190Glu	missense_variant	Exon 2 of 6	1	NM_002706.6	ENSP00000282412.4
ENSG00000285542	ENST00000649044.1	n.568C>G		non_coding_transcript_exon_variant	Exon 2 of 15			ENSP00000497083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 29, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.568C>G (p.Q190E) alteration is located in exon 2 (coding exon 1) of the PPM1B gene. This alteration results from a C to G substitution at nucleotide position 568, causing the glutamine (Q) at amino acid position 190 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	.;.;T;.;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D;D;D;D
M_CAP	Benign	0.035	D
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	.;L;L;L;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-2.2	N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.046	D;D;D;D;D
Sift4G	Benign	0.085	T;T;T;T;T
Polyphen		0.26, 0.11	.;.;B;B;.
Vest4		0.70, 0.76, 0.70
MutPred		0.70		Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);Loss of MoRF binding (P = 0.0269);
MVP		0.66
MPC		0.43
ClinPred		0.83	D
GERP RS		5.7
Varity_R		0.76
gMVP		0.78

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44428906;