rs1560092

Variant names:

• chr19-52207761-G-T
• rs1560092
• NM_014225.6:c.270+1698G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014225.6(PPP2R1A):​c.270+1698G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,976 control chromosomes in the GnomAD database, including 14,446 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.42 (14446 hom., cov: 32)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.652
• Publications: 8 publications found

Genes affected

PPP2R1A (HGNC:9302): (protein phosphatase 2 scaffold subunit Aalpha) 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 an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described. [provided by RefSeq, Apr 2010]

PPP2R1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Houge-Janssens syndrome 2

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R1A	NM_014225.6	c.270+1698G>T		intron_variant	Intron 3 of 14	ENST00000322088.11	NP_055040.2
PPP2R1A	NM_001363656.2	c.-268+1698G>T		intron_variant	Intron 3 of 14		NP_001350585.1
PPP2R1A	NR_033500.2	n.215-3499G>T		intron_variant	Intron 2 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.270+1698G>T		intron_variant	Intron 3 of 14	1	NM_014225.6	ENSP00000324804.6

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64407 AN: 151858 Hom.: 14446 Cov.: 32

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.455

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.424 AC: 64431 AN: 151976 Hom.: 14446 Cov.: 32 AF XY: 0.428 AC XY: 31791 AN XY: 74274

African (AFR) AF: 0.274 AC: 11352 AN: 41460

American (AMR) AF: 0.517 AC: 7894 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.445 AC: 1544 AN: 3470

East Asian (EAS) AF: 0.596 AC: 3077 AN: 5164

South Asian (SAS) AF: 0.525 AC: 2527 AN: 4816

European-Finnish (FIN) AF: 0.455 AC: 4796 AN: 10532

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.468 AC: 31799 AN: 67940

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.461 Hom.: 35302

Bravo AF: 0.426

Asia WGS AF: 0.519 AC: 1803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.78
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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: rs1560092; hg19: chr19-52711014;