rs1746595

Variant names:

• chr14-101849579-A-G
• rs1746595
• NM_001352913.2:c.260-7107A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-101849579-A-G
• chr14-101849579-A-T

Variant summary

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

The ENST00000694906.1(PPP2R5C):​c.260-7107A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 151,146 control chromosomes in the GnomAD database, including 2,986 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 0.22 (2986 hom., cov: 31)
• Consequence: PPP2R5C ENST00000694906.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 5 publications found

Genes affected

PPP2R5C (HGNC:9311): (protein phosphatase 2 regulatory subunit B'gamma) The product of this gene belongs to the phosphatase 2A regulatory subunit B family. 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. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a gamma isoform of the regulatory subunit B56 subfamily. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

PPP2R5C Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000694906.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	NM_001352913.2	MANE Select	c.260-7107A>G		intron	N/A	NP_001339842.1
	PPP2R5C	NM_001161725.2		c.188-7107A>G		intron	N/A	NP_001155197.1
	PPP2R5C	NM_001352914.2		c.275-7107A>G		intron	N/A	NP_001339843.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5C	ENST00000694906.1	MANE Select	c.260-7107A>G		intron	N/A	ENSP00000511581.1
	PPP2R5C	ENST00000334743.9	TSL:1	c.95-7107A>G		intron	N/A	ENSP00000333905.4
	PPP2R5C	ENST00000350249.7	TSL:1	c.95-7107A>G		intron	N/A	ENSP00000262239.5

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33363 AN: 151026 Hom.: 2982 Cov.: 31

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.0855

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.231

Gnomad EAS AF: 0.0985

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.221 AC: 33393 AN: 151146 Hom.: 2986 Cov.: 31 AF XY: 0.216 AC XY: 15965 AN XY: 73842

African (AFR) AF: 0.252 AC: 10357 AN: 41122

American (AMR) AF: 0.195 AC: 2961 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.231 AC: 801 AN: 3462

East Asian (EAS) AF: 0.0987 AC: 510 AN: 5168

South Asian (SAS) AF: 0.156 AC: 748 AN: 4802

European-Finnish (FIN) AF: 0.175 AC: 1837 AN: 10480

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15582 AN: 67634

Other (OTH) AF: 0.220 AC: 460 AN: 2094

Alfa AF: 0.225 Hom.: 5022

Bravo AF: 0.230

Asia WGS AF: 0.134 AC: 467 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.83
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs1746595; hg19: chr14-102315916;