chr14-101836035-A-G

Variant names:

• chr14-101836035-A-G
• rs10431745
• NM_001352913.2:c.260-20651A>G

Variant summary

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

The NM_001352913.2(PPP2R5C):​c.260-20651A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0756 in 597,446 control chromosomes in the GnomAD database, including 2,172 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 0.092 (756 hom., cov: 33)
  • Exomes 𝑓: 0.070 (1416 hom.)
• Consequence: PPP2R5C NM_001352913.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• Publications: 1 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

ENSG00000256705 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001352913.2. 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.260-20651A>G		intron	N/A	NP_001339842.1
	PPP2R5C	NM_001161725.2		c.187+16950A>G		intron	N/A	NP_001155197.1
	PPP2R5C	NM_001352914.2		c.275-20651A>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.260-20651A>G		intron	N/A	ENSP00000511581.1
	PPP2R5C	ENST00000334743.9	TSL:1	c.95-20651A>G		intron	N/A	ENSP00000333905.4
	PPP2R5C	ENST00000350249.7	TSL:1	c.95-20651A>G		intron	N/A	ENSP00000262239.5

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13976 AN: 152194 Hom.: 752 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.0458

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.0199

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0880

GnomAD4 exome AF: 0.0700 AC: 31167 AN: 445134 Hom.: 1416 AF XY: 0.0665 AC XY: 15557 AN XY: 234076

African (AFR) AF: 0.123 AC: 1523 AN: 12374

American (AMR) AF: 0.167 AC: 3123 AN: 18674

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 590 AN: 13778

East Asian (EAS) AF: 0.101 AC: 3133 AN: 31088

South Asian (SAS) AF: 0.0181 AC: 788 AN: 43462

European-Finnish (FIN) AF: 0.0654 AC: 1944 AN: 29746

Middle Eastern (MID) AF: 0.0358 AC: 71 AN: 1984

European-Non Finnish (NFE) AF: 0.0671 AC: 17980 AN: 268048

Other (OTH) AF: 0.0776 AC: 2015 AN: 25980

GnomAD4 genome AF: 0.0920 AC: 14015 AN: 152312 Hom.: 756 Cov.: 33 AF XY: 0.0908 AC XY: 6766 AN XY: 74488

African (AFR) AF: 0.130 AC: 5387 AN: 41568

American (AMR) AF: 0.142 AC: 2178 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0458 AC: 159 AN: 3470

East Asian (EAS) AF: 0.137 AC: 709 AN: 5188

South Asian (SAS) AF: 0.0201 AC: 97 AN: 4832

European-Finnish (FIN) AF: 0.0607 AC: 644 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0671 AC: 4563 AN: 68030

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0883 Hom.: 124

Bravo AF: 0.103

Asia WGS AF: 0.0880 AC: 307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	5.6
DANN	Benign	0.92
PhyloP100		-0.032
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: rs10431745; hg19: chr14-102302372;