19-52212538-G-C

Variant names:

• chr19-52212538-G-C
• rs10403202
• NM_014225.6:c.504-148G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014225.6(PPP2R1A):​c.504-148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000125 in 801,192 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: PPP2R1A NM_014225.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R1A	NM_014225.6	c.504-148G>C		intron_variant	Intron 4 of 14	ENST00000322088.11	NP_055040.2
PPP2R1A	NM_001363656.2	c.-34-148G>C		intron_variant	Intron 4 of 14		NP_001350585.1
PPP2R1A	NR_033500.2	n.448-148G>C		intron_variant	Intron 3 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R1A	ENST00000322088.11	c.504-148G>C		intron_variant	Intron 4 of 14	1	NM_014225.6	ENSP00000324804.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000125 AC: 1 AN: 801192 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 404230

African (AFR) AF: 0.00 AC: 0 AN: 19054

American (AMR) AF: 0.00 AC: 0 AN: 22328

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16456

East Asian (EAS) AF: 0.00 AC: 0 AN: 32436

South Asian (SAS) AF: 0.00 AC: 0 AN: 54824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30744

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2700

European-Non Finnish (NFE) AF: 0.00000171 AC: 1 AN: 585054

Other (OTH) AF: 0.00 AC: 0 AN: 37596

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.46
PhyloP100		-2.9

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs10403202; hg19: chr19-52715791;