chr8-26360816-C-T

Variant names:

• chr8-26360816-C-T
• rs12682345
• NM_002717.4:c.460-158C>T

Variant summary

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

The NM_002717.4(PPP2R2A):​c.460-158C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.723 in 626,220 control chromosomes in the GnomAD database, including 164,880 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 0.73 (40367 hom., cov: 33)
  • Exomes 𝑓: 0.72 (124513 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• Publications: 5 publications found

Genes affected

PPP2R2A (HGNC:9304): (protein phosphatase 2 regulatory subunit Balpha) The product of this gene belongs to the phosphatase 2 regulatory subunit B family. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an alpha isoform of the regulatory subunit B55 subfamily. Alternatively spliced transcript variants have been described. [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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R2A	NM_002717.4	c.460-158C>T		intron_variant	Intron 5 of 9	ENST00000380737.8	NP_002708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.460-158C>T		intron_variant	Intron 5 of 9	1	NM_002717.4	ENSP00000370113.3

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110353 AN: 152036 Hom.: 40317 Cov.: 33

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.651

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.876

Gnomad SAS AF: 0.756

Gnomad FIN AF: 0.785

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.708

GnomAD4 exome AF: 0.722 AC: 342343 AN: 474066 Hom.: 124513 Cov.: 6 AF XY: 0.722 AC XY: 177096 AN XY: 245420

African (AFR) AF: 0.748 AC: 7689 AN: 10286

American (AMR) AF: 0.616 AC: 6543 AN: 10622

Ashkenazi Jewish (ASJ) AF: 0.580 AC: 7595 AN: 13092

East Asian (EAS) AF: 0.869 AC: 22320 AN: 25686

South Asian (SAS) AF: 0.742 AC: 24933 AN: 33616

European-Finnish (FIN) AF: 0.773 AC: 22845 AN: 29562

Middle Eastern (MID) AF: 0.627 AC: 1231 AN: 1964

European-Non Finnish (NFE) AF: 0.714 AC: 230665 AN: 323138

Other (OTH) AF: 0.710 AC: 18522 AN: 26100

GnomAD4 genome AF: 0.726 AC: 110458 AN: 152154 Hom.: 40367 Cov.: 33 AF XY: 0.729 AC XY: 54267 AN XY: 74396

African (AFR) AF: 0.759 AC: 31508 AN: 41512

American (AMR) AF: 0.650 AC: 9938 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2036 AN: 3468

East Asian (EAS) AF: 0.876 AC: 4542 AN: 5184

South Asian (SAS) AF: 0.756 AC: 3651 AN: 4828

European-Finnish (FIN) AF: 0.785 AC: 8300 AN: 10578

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48210 AN: 67986

Other (OTH) AF: 0.712 AC: 1506 AN: 2114

Alfa AF: 0.715 Hom.: 5482

Bravo AF: 0.714

Asia WGS AF: 0.792 AC: 2752 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.45
PhyloP100		1.0
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: rs12682345; hg19: chr8-26218332;