rs1805076

Variant names:

• chr11-111764842-C-T
• rs1805076
• NM_002716.5:c.269G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 1P and 2B. PP5 BP4 BS2_Supporting

The NM_002716.5(PPP2R1B):​c.269G>A​(p.Gly90Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,614,070 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency:
  • Genomes: 𝑓 0.0069 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (102 hom.)
• Consequence: PPP2R1B NM_002716.5 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 2.53
• Publications: 25 publications found

Genes affected

PPP2R1B (HGNC:9303): (protein phosphatase 2 scaffold subunit Abeta) This gene encodes a constant regulatory subunit of protein phosphatase 2. 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 constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes a beta isoform of the constant regulatory subunit A. Mutations in this gene have been associated with some lung and colon cancers. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PP5: Variant 11-111764842-C-T is Pathogenic according to our data. Variant chr11-111764842-C-T is described in ClinVar as Pathogenic. ClinVar VariationId is 6621.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (MetaRNN=0.017846048). . Strength limited to SUPPORTING due to the PP5.
• BS2: High AC in GnomAd4 at 1053 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002716.5. 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
	PPP2R1B	NM_002716.5	MANE Select	c.269G>A	p.Gly90Asp	missense	Exon 3 of 15	NP_002707.3
	PPP2R1B	NM_181699.3		c.269G>A	p.Gly90Asp	missense	Exon 3 of 16	NP_859050.1	P30154-2
	PPP2R1B	NM_001177562.2		c.269G>A	p.Gly90Asp	missense	Exon 3 of 14	NP_001171033.1	P30154-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R1B	ENST00000527614.6	TSL:1 MANE Select	c.269G>A	p.Gly90Asp	missense	Exon 3 of 15	ENSP00000437193.1	P30154-1
	PPP2R1B	ENST00000311129.9	TSL:1	c.269G>A	p.Gly90Asp	missense	Exon 3 of 16	ENSP00000311344.5	P30154-2
	PPP2R1B	ENST00000925452.1		c.269G>A	p.Gly90Asp	missense	Exon 3 of 15	ENSP00000595511.1

Frequencies

GnomAD3 genomes AF: 0.00691 AC: 1052 AN: 152178 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00227

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00443

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.00718

GnomAD2 exomes AF: 0.00652 AC: 1638 AN: 251370 AF XY: 0.00676

Gnomad AFR exome AF: 0.00228

Gnomad AMR exome AF: 0.00173

Gnomad ASJ exome AF: 0.00179

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00389

Gnomad NFE exome AF: 0.0119

Gnomad OTH exome AF: 0.00570

GnomAD4 exome AF: 0.0109 AC: 15894 AN: 1461774 Hom.: 102 Cov.: 30 AF XY: 0.0106 AC XY: 7720 AN XY: 727182

African (AFR) AF: 0.00197 AC: 66 AN: 33478

American (AMR) AF: 0.00206 AC: 92 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00188 AC: 49 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00166 AC: 143 AN: 86256

European-Finnish (FIN) AF: 0.00412 AC: 220 AN: 53358

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.0134 AC: 14862 AN: 1111974

Other (OTH) AF: 0.00740 AC: 447 AN: 60392

GnomAD4 genome AF: 0.00691 AC: 1053 AN: 152296 Hom.: 6 Cov.: 32 AF XY: 0.00655 AC XY: 488 AN XY: 74470

African (AFR) AF: 0.00226 AC: 94 AN: 41564

American (AMR) AF: 0.00216 AC: 33 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00186 AC: 9 AN: 4826

European-Finnish (FIN) AF: 0.00443 AC: 47 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0124 AC: 844 AN: 68022

Other (OTH) AF: 0.00711 AC: 15 AN: 2110

Alfa AF: 0.0112 Hom.: 32

Bravo AF: 0.00672

TwinsUK AF: 0.0108 AC: 40

ALSPAC AF: 0.0158 AC: 61

ESP6500AA AF: 0.00273 AC: 12

ESP6500EA AF: 0.0122 AC: 105

ExAC AF: 0.00627 AC: 761

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Pathogenic

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
1	-	-	Lung carcinoma (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	21
DANN	Benign	0.63
DEOGEN2	Benign	0.0029	T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.94	D
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.94	N
PhyloP100		2.5
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	0.98	N
REVEL	Benign	0.079
Sift	Benign	0.20	T
Sift4G	Benign	0.37	T
Polyphen		0.0	B
Vest4		0.34
MVP		0.31
MPC		0.28
ClinPred		0.011	T
GERP RS		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.096
gMVP		0.44
Mutation Taster		=277/23	disease causing (ClinVar)

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: rs1805076; hg19: chr11-111635566; COSMIC: COSV100232045; COSMIC: COSV100232045;