5-134221625-A-C

Variant names:

• chr5-134221625-A-C
• rs2868600
• NM_002715.4:c.102+4135T>G

Variant summary

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

The NM_002715.4(PPP2CA):​c.102+4135T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,006 control chromosomes in the GnomAD database, including 45,217 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 0.77 (45217 hom., cov: 31)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.401
• Publications: 2 publications found

Genes affected

PPP2CA (HGNC:9299): (protein phosphatase 2 catalytic subunit alpha) This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A 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. This gene encodes an alpha isoform of the catalytic subunit. [provided by RefSeq, Jul 2008]

PPP2CA Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Houge-Janssens syndrome 3

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ENSG00000272772 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002715.4. 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
	PPP2CA	NM_002715.4	MANE Select	c.102+4135T>G		intron	N/A	NP_002706.1	B3KUN1
	PPP2CA	NM_001355019.2		c.-94+3584T>G		intron	N/A	NP_001341948.1	B3KQ51
	PPP2CA	NR_149151.2		n.346+3584T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2CA	ENST00000481195.6	TSL:1 MANE Select	c.102+4135T>G		intron	N/A	ENSP00000418447.1	P67775-1
	ENSG00000272772	ENST00000519718.2	TSL:5	c.102+4135T>G		intron	N/A	ENSP00000430774.2	E5RI56
	ENSG00000273345	ENST00000703317.1		n.*74-15494T>G		intron	N/A	ENSP00000515260.1	A0A8V8TQA6

Frequencies

GnomAD3 genomes AF: 0.768 AC: 116575 AN: 151888 Hom.: 45194 Cov.: 31

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.734

Gnomad MID AF: 0.774

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.756

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

GnomAD4 genome AF: 0.767 AC: 116647 AN: 152006 Hom.: 45217 Cov.: 31 AF XY: 0.758 AC XY: 56281 AN XY: 74276

African (AFR) AF: 0.757 AC: 31368 AN: 41456

American (AMR) AF: 0.646 AC: 9862 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2690 AN: 3472

East Asian (EAS) AF: 0.553 AC: 2860 AN: 5168

South Asian (SAS) AF: 0.742 AC: 3572 AN: 4812

European-Finnish (FIN) AF: 0.734 AC: 7728 AN: 10534

Middle Eastern (MID) AF: 0.791 AC: 231 AN: 292

European-Non Finnish (NFE) AF: 0.823 AC: 55924 AN: 67984

Other (OTH) AF: 0.755 AC: 1593 AN: 2110

Alfa AF: 0.760 Hom.: 2598

Bravo AF: 0.756

Asia WGS AF: 0.679 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.5
DANN	Benign	0.59
PhyloP100		0.40
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: rs2868600; hg19: chr5-133557316;