5-134213137-T-C

Variant names:

• chr5-134213137-T-C
• rs4958177
• NM_002715.4:c.103-7006A>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.103-7006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.873 in 152,240 control chromosomes in the GnomAD database, including 58,311 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 0.87 (58311 hom., cov: 32)
• Consequence: PPP2CA NM_002715.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.379
• Publications: 1 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: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000272772 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.901 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.103-7006A>G		intron	N/A	NP_002706.1	B3KUN1
	PPP2CA	NM_001355019.2		c.-93-7006A>G		intron	N/A	NP_001341948.1	B3KQ51
	PPP2CA	NR_149151.2		n.347-7006A>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.103-7006A>G		intron	N/A	ENSP00000418447.1	P67775-1
	ENSG00000272772	ENST00000519718.2	TSL:5	c.102+12623A>G		intron	N/A	ENSP00000430774.2	E5RI56
	ENSG00000273345	ENST00000703317.1		n.*74-7006A>G		intron	N/A	ENSP00000515260.1	A0A8V8TQA6

Frequencies

GnomAD3 genomes AF: 0.873 AC: 132759 AN: 152120 Hom.: 58264 Cov.: 32

Gnomad AFR AF: 0.909

Gnomad AMI AF: 0.930

Gnomad AMR AF: 0.804

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.902

Gnomad NFE AF: 0.888

Gnomad OTH AF: 0.878

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

GnomAD4 genome AF: 0.873 AC: 132861 AN: 152240 Hom.: 58311 Cov.: 32 AF XY: 0.868 AC XY: 64622 AN XY: 74426

African (AFR) AF: 0.909 AC: 37754 AN: 41544

American (AMR) AF: 0.803 AC: 12279 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2981 AN: 3470

East Asian (EAS) AF: 0.607 AC: 3141 AN: 5172

South Asian (SAS) AF: 0.841 AC: 4053 AN: 4820

European-Finnish (FIN) AF: 0.874 AC: 9267 AN: 10602

Middle Eastern (MID) AF: 0.918 AC: 270 AN: 294

European-Non Finnish (NFE) AF: 0.888 AC: 60411 AN: 68024

Other (OTH) AF: 0.878 AC: 1857 AN: 2116

Alfa AF: 0.886 Hom.: 7281

Bravo AF: 0.866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.81
PhyloP100		-0.38
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4958177; hg19: chr5-133548828;