chr2-27388602-A-G

Variant names:

• chr2-27388602-A-G
• rs7594812
• NM_177983.3:c.121-1444T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_177983.3(PPM1G):​c.121-1444T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,634 control chromosomes in the GnomAD database, including 18,598 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 (18598 hom., cov: 31)
• Consequence: PPM1G NM_177983.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177983.3. 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
	PPM1G	NM_177983.3	MANE Select	c.121-1444T>C		intron	N/A	NP_817092.1	Q6IAU5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1G	ENST00000344034.5	TSL:1 MANE Select	c.121-1444T>C		intron	N/A	ENSP00000342778.4	O15355
	PPM1G	ENST00000948123.1		c.121-1444T>C		intron	N/A	ENSP00000618182.1
	PPM1G	ENST00000893256.1		c.121-1444T>C		intron	N/A	ENSP00000563315.1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71480 AN: 151514 Hom.: 18548 Cov.: 31

Gnomad AFR AF: 0.691

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.156

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.413

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.472 AC: 71599 AN: 151634 Hom.: 18598 Cov.: 31 AF XY: 0.471 AC XY: 34860 AN XY: 74084

African (AFR) AF: 0.691 AC: 28591 AN: 41360

American (AMR) AF: 0.475 AC: 7232 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3468

East Asian (EAS) AF: 0.156 AC: 793 AN: 5076

South Asian (SAS) AF: 0.434 AC: 2085 AN: 4800

European-Finnish (FIN) AF: 0.430 AC: 4522 AN: 10528

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 26027 AN: 67874

Other (OTH) AF: 0.417 AC: 878 AN: 2104

Alfa AF: 0.447 Hom.: 2117

Bravo AF: 0.483

Asia WGS AF: 0.366 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.5
DANN	Benign	0.53
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs7594812; hg19: chr2-27611469;