rs11146169

Positions:

• chr10-131932772-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_018461.5(PPP2R2D):​c.101-1686A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000773 in 151,402 control chromosomes in the GnomAD database, including 1 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 0.00077 (1 hom., cov: 31)
• Consequence: PPP2R2D NM_018461.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

Genes affected

PPP2R2D (HGNC:23732): (protein phosphatase 2 regulatory subunit Bdelta) Predicted to enable protein phosphatase regulator activity. Predicted to be involved in exit from mitosis and peptidyl-serine dephosphorylation. Predicted to be part of protein phosphatase type 2A complex. Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000773 (117/151402) while in subpopulation EAS AF= 0.0209 (108/5172). AF 95% confidence interval is 0.0177. There are 1 homozygotes in gnomad4. There are 73 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP2R2D	NM_018461.5	c.101-1686A>G		intron_variant		ENST00000455566.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP2R2D	ENST00000455566.6	c.101-1686A>G		intron_variant		1	NM_018461.5	P1
PPP2R2D	ENST00000470416.5	c.*904-1686A>G		intron_variant, NMD_transcript_variant		1
PPP2R2D	ENST00000616467.4	c.101-1686A>G		intron_variant, NMD_transcript_variant		1
PPP2R2D	ENST00000482010.6	c.66-1686A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000773 AC: 117 AN: 151296 Hom.: 1 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0208

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000961

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000484

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

GnomAD4 genome AF: 0.000773 AC: 117 AN: 151402 Hom.: 1 Cov.: 31 AF XY: 0.000987 AC XY: 73 AN XY: 73994

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0209

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.0000961

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000480

Alfa AF: 0.000233 Hom.: 0

Bravo AF: 0.00123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.46

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11146169; hg19: chr10-133746276;