8-26363964-C-G

Variant names:

• chr8-26363964-C-G
• rs74731529
• NM_002717.4:c.972+74C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1798 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002717.4. 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
	PPP2R2A	NM_002717.4	MANE Select	c.972+74C>G		intron	N/A	NP_002708.1	A0A140VJT0
	PPP2R2A	NM_001177591.2		c.1002+74C>G		intron	N/A	NP_001171062.1	P63151-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R2A	ENST00000380737.8	TSL:1 MANE Select	c.972+74C>G		intron	N/A	ENSP00000370113.3	P63151-1
	PPP2R2A	ENST00000315985.7	TSL:2	c.1002+74C>G		intron	N/A	ENSP00000325074.7	P63151-2
	PPP2R2A	ENST00000919755.1		c.894+74C>G		intron	N/A	ENSP00000589814.1

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

African (AFR) AF: 0.00196 AC: 54 AN: 27606

American (AMR) AF: 0.0112 AC: 325 AN: 28904

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 232 AN: 18560

East Asian (EAS) AF: 0.0000268 AC: 1 AN: 37376

South Asian (SAS) AF: 0.00345 AC: 177 AN: 51374

European-Finnish (FIN) AF: 0.0168 AC: 737 AN: 43940

Middle Eastern (MID) AF: 0.0105 AC: 35 AN: 3332

European-Non Finnish (NFE) AF: 0.0192 AC: 18037 AN: 940458

Other (OTH) AF: 0.0157 AC: 779 AN: 49724

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

African (AFR) AF: 0.00281 AC: 117 AN: 41564

American (AMR) AF: 0.0152 AC: 232 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 43 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4826

European-Finnish (FIN) AF: 0.0155 AC: 164 AN: 10602

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1182 AN: 68026

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.00781 Hom.: 1

Bravo AF: 0.0124

Asia WGS AF: 0.00173 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.82
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism

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: rs74731529; hg19: chr8-26221480;