10-131956344-C-G

Variant names:

• chr10-131956344-C-G
• rs7199
• ENST00000470416.5:n.*2546C>G

Variant summary

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

The ENST00000470416.5(PPP2R2D):​n.*2546C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 988,370 control chromosomes in the GnomAD database, including 31,315 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 0.28 (6028 hom., cov: 33)
  • Exomes 𝑓: 0.24 (25287 hom.)
• Consequence: PPP2R2D ENST00000470416.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 7 publications found

Genes affected

PPP2R2D (HGNC:23732): (protein phosphatase 2 regulatory subunit Bdelta) Predicted to enable protein phosphatase regulator activity. Predicted to be involved in exit from mitosis and peptidyl-serine dephosphorylation. Predicted to be part of protein phosphatase type 2A complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2D	NM_018461.5	c.*381C>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000455566.6	NP_060931.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2D	ENST00000455566.6	c.*381C>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_018461.5	ENSP00000399970.2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42398 AN: 151966 Hom.: 6019 Cov.: 33

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.278

GnomAD4 exome AF: 0.245 AC: 204718 AN: 836286 Hom.: 25287 Cov.: 30 AF XY: 0.244 AC XY: 94374 AN XY: 386304

African (AFR) AF: 0.291 AC: 4636 AN: 15928

American (AMR) AF: 0.280 AC: 303 AN: 1082

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1813 AN: 5300

East Asian (EAS) AF: 0.473 AC: 1802 AN: 3808

South Asian (SAS) AF: 0.279 AC: 4611 AN: 16506

European-Finnish (FIN) AF: 0.238 AC: 93 AN: 390

Middle Eastern (MID) AF: 0.300 AC: 490 AN: 1634

European-Non Finnish (NFE) AF: 0.240 AC: 183729 AN: 764136

Other (OTH) AF: 0.263 AC: 7241 AN: 27502

GnomAD4 genome AF: 0.279 AC: 42444 AN: 152084 Hom.: 6028 Cov.: 33 AF XY: 0.281 AC XY: 20915 AN XY: 74326

African (AFR) AF: 0.287 AC: 11903 AN: 41484

American (AMR) AF: 0.296 AC: 4532 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.355 AC: 1230 AN: 3466

East Asian (EAS) AF: 0.447 AC: 2300 AN: 5146

South Asian (SAS) AF: 0.291 AC: 1404 AN: 4818

European-Finnish (FIN) AF: 0.277 AC: 2929 AN: 10582

Middle Eastern (MID) AF: 0.277 AC: 81 AN: 292

European-Non Finnish (NFE) AF: 0.253 AC: 17217 AN: 67988

Other (OTH) AF: 0.278 AC: 587 AN: 2114

Alfa AF: 0.140 Hom.: 252

Bravo AF: 0.283

Asia WGS AF: 0.339 AC: 1180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.60
PhyloP100		-0.031
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs7199; hg19: chr10-133769848; COSMIC: COSV70778750; COSMIC: COSV70778750;