rs201318610

Variant names:

• chr2-44202030-C-A
• NM_002706.6:c.831C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-44202030-C-A
• chr2-44202030-C-G

Variant summary

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

The NM_002706.6(PPM1B):​c.831C>A​(p.Asp277Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,415,222 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: PPM1B NM_002706.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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.831C>A	p.Asp277Glu	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.831C>A	p.Asp277Glu	missense_variant	Exon 2 of 6	1	NM_002706.6	ENSP00000282412.4
ENSG00000285542	ENST00000649044.1	n.831C>A		non_coding_transcript_exon_variant	Exon 2 of 15			ENSP00000497083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1415222 Hom.: 0 Cov.: 31 AF XY: 0.00000143 AC XY: 1 AN XY: 699390

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.17e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	.;.;T;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	.;L;L;L
PrimateAI	Pathogenic	0.83	D
PROVEAN	Uncertain	-3.5	D;D;D;D
REVEL	Benign	0.24
Sift	Benign	0.041	D;D;D;D
Sift4G	Benign	0.088	T;T;T;T
Polyphen		0.81, 0.28	.;.;P;B
Vest4		0.75, 0.79, 0.74
MutPred		0.56		Gain of ubiquitination at K282 (P = 0.1446);Gain of ubiquitination at K282 (P = 0.1446);Gain of ubiquitination at K282 (P = 0.1446);Gain of ubiquitination at K282 (P = 0.1446);
MVP		0.67
MPC		0.54
ClinPred		0.98	D
GERP RS		5.9
Varity_R		0.84
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-44429169;