rs1647284

Positions:

• chr2-27385248-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177983.3(PPM1G):​c.410-160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.399 in 724,412 control chromosomes in the GnomAD database, including 63,091 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.47 (18597 hom., cov: 32)
  • Exomes 𝑓: 0.38 (44494 hom.)
• Consequence: PPM1G NM_177983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

Genes affected

PPM1G (HGNC:9278): (protein phosphatase, Mg2+/Mn2+ dependent 1G) 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 is found to be responsible for the dephosphorylation of Pre-mRNA splicing factors, which is important for the formation of functional spliceosome. Studies of a similar gene in mice suggested a role of this phosphatase in regulating cell cycle progression. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPM1G	NM_177983.3	c.410-160G>A		intron_variant		ENST00000344034.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPM1G	ENST00000344034.5	c.410-160G>A		intron_variant		1	NM_177983.3	P1
PPM1G	ENST00000472077.1	n.2164G>A		non_coding_transcript_exon_variant	2/8	2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71493 AN: 151890 Hom.: 18549 Cov.: 32

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.220

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.154

Gnomad SAS AF: 0.425

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.380 AC: 217550 AN: 572404 Hom.: 44494 Cov.: 8 AF XY: 0.381 AC XY: 110986 AN XY: 291552

Gnomad4 AFR exome AF: 0.694

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.333

Gnomad4 EAS exome AF: 0.125

Gnomad4 SAS exome AF: 0.408

Gnomad4 FIN exome AF: 0.429

Gnomad4 NFE exome AF: 0.378

Gnomad4 OTH exome AF: 0.389

GnomAD4 genome AF: 0.471 AC: 71607 AN: 152008 Hom.: 18597 Cov.: 32 AF XY: 0.469 AC XY: 34842 AN XY: 74268

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.474

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.154

Gnomad4 SAS AF: 0.426

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.415

Alfa AF: 0.441 Hom.: 2531

Bravo AF: 0.483

Asia WGS AF: 0.363 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.81
DANN	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs1647284; hg19: chr2-27608115;