11-111752218-C-T

Position:

• chr11-111752218-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002716.5(PPP2R1B):​c.1279G>A​(p.Ala427Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP2R1B NM_002716.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.24

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19613844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP2R1B	NM_002716.5	c.1279G>A	p.Ala427Thr	missense_variant	10/15	ENST00000527614.6	NP_002707.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP2R1B	ENST00000527614.6	c.1279G>A	p.Ala427Thr	missense_variant	10/15	1	NM_002716.5	ENSP00000437193.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.1279G>A (p.A427T) alteration is located in exon 10 (coding exon 10) of the PPP2R1B gene. This alteration results from a G to A substitution at nucleotide position 1279, causing the alanine (A) at amino acid position 427 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	.;.;T;.;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.95	D;D;D;D;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.075	N;.;N;.;.
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	-1.0	N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.41	T;T;T;T;T
Sift4G	Benign	0.54	T;T;T;T;T
Polyphen		0.0	B;.;B;.;.
Vest4		0.25
MutPred		0.31		Gain of ubiquitination at K428 (P = 0.1008);.;Gain of ubiquitination at K428 (P = 0.1008);.;.;
MVP		0.35
MPC		0.21
ClinPred		0.40	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-111622942;