chr8-26363964-C-G

Position:

• chr8-26363964-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002717.4(PPP2R2A):​c.972+74C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0164 in 1,353,562 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (14 hom., cov: 32)
  • Exomes 𝑓: 0.017 (195 hom.)
• Consequence: PPP2R2A NM_002717.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.418

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 8-26363964-C-G is Benign according to our data. Variant chr8-26363964-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1679067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0118 (1798/152288) while in subpopulation NFE AF= 0.0174 (1182/68026). AF 95% confidence interval is 0.0166. There are 14 homozygotes in gnomad4. There are 815 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1798 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2A	NM_002717.4	c.972+74C>G		intron_variant		ENST00000380737.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2A	ENST00000380737.8	c.972+74C>G		intron_variant		1	NM_002717.4	P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1798 AN: 152170 Hom.: 14 Cov.: 32

Gnomad AFR AF: 0.00282

Gnomad AMI AF: 0.0253

Gnomad AMR AF: 0.0152

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.0170 AC: 20377 AN: 1201274 Hom.: 195 AF XY: 0.0166 AC XY: 9756 AN XY: 588164

Gnomad4 AFR exome AF: 0.00196

Gnomad4 AMR exome AF: 0.0112

Gnomad4 ASJ exome AF: 0.0125

Gnomad4 EAS exome AF: 0.0000268

Gnomad4 SAS exome AF: 0.00345

Gnomad4 FIN exome AF: 0.0168

Gnomad4 NFE exome AF: 0.0192

Gnomad4 OTH exome AF: 0.0157

GnomAD4 genome AF: 0.0118 AC: 1798 AN: 152288 Hom.: 14 Cov.: 32 AF XY: 0.0109 AC XY: 815 AN XY: 74458

Gnomad4 AFR AF: 0.00281

Gnomad4 AMR AF: 0.0152

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.0155

Gnomad4 NFE AF: 0.0174

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00781 Hom.: 1

Bravo AF: 0.0124

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Hereditary breast ovarian cancer syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Apr 19, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.82

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: rs74731529; hg19: chr8-26221480;