11-111742068-G-A

Variant names:

• chr11-111742068-G-A
• rs780104936
• NM_002716.5:c.1774C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_002716.5(PPP2R1B):​c.1774C>T​(p.Gln592*) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,902 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: PPP2R1B NM_002716.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.57
• Publications: 0 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.

• BS2: High AC in GnomAdExome4 at 6 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.1774C>T	p.Gln592*	stop_gained	Exon 14 of 15	NP_002707.3
	PPP2R1B	NM_181699.3		c.1774C>T	p.Gln592*	stop_gained	Exon 14 of 16	NP_859050.1	P30154-2
	PPP2R1B	NM_181700.2		c.1582C>T	p.Gln528*	stop_gained	Exon 12 of 14	NP_859051.1	P30154-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R1B	ENST00000527614.6	TSL:1 MANE Select	c.1774C>T	p.Gln592*	stop_gained	Exon 14 of 15	ENSP00000437193.1	P30154-1
	PPP2R1B	ENST00000311129.9	TSL:1	c.1774C>T	p.Gln592*	stop_gained	Exon 14 of 16	ENSP00000311344.5	P30154-2
	PPP2R1B	ENST00000426998.6	TSL:2	c.1582C>T	p.Gln528*	stop_gained	Exon 12 of 14	ENSP00000410671.2	P30154-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251370 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1460902 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726820

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26124

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53372

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111184

Other (OTH) AF: 0.00 AC: 0 AN: 60366

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000247 AC: 3

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.58	D
BayesDel_noAF	Pathogenic	0.65
CADD	Pathogenic	40
DANN	Uncertain	0.98
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	1.0	D
PhyloP100		9.6
Vest4		0.97
ClinPred		0.99	D
GERP RS		5.5
Mutation Taster		=32/168	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs780104936; hg19: chr11-111612792;