rs7410608

Variant names:

• chr22-50420384-G-C
• rs7410608
• NM_001242898.2:c.845+922G>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_001242898.2(PPP6R2):​c.845+922G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,012 control chromosomes in the GnomAD database, including 12,878 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 0.40 (12878 hom., cov: 33)
• Consequence: PPP6R2 NM_001242898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.175
• Publications: 7 publications found

Genes affected

PPP6R2 (HGNC:19253): (protein phosphatase 6 regulatory subunit 2) The protein encoded by this gene is a regulatory protein for the protein phosphatase-6 catalytic subunit. Together, these proteins act as a significant T-loop phosphatase for Aurora A, an essential mitotic kinase. Loss of function of either the regulatory or catalytic subunit of protein phosphatase-6 interferes with spindle formation and chromosome alignment. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP6R2	NM_001242898.2	c.845+922G>C		intron_variant	Intron 8 of 23	ENST00000612753.5	NP_001229827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP6R2	ENST00000612753.5	c.845+922G>C		intron_variant	Intron 8 of 23	2	NM_001242898.2	ENSP00000478417.1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61259 AN: 151894 Hom.: 12864 Cov.: 33

Gnomad AFR AF: 0.436

Gnomad AMI AF: 0.386

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.412

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.322

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.403 AC: 61326 AN: 152012 Hom.: 12878 Cov.: 33 AF XY: 0.410 AC XY: 30454 AN XY: 74278

African (AFR) AF: 0.436 AC: 18060 AN: 41450

American (AMR) AF: 0.434 AC: 6622 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.346 AC: 1199 AN: 3468

East Asian (EAS) AF: 0.745 AC: 3860 AN: 5178

South Asian (SAS) AF: 0.410 AC: 1974 AN: 4810

European-Finnish (FIN) AF: 0.435 AC: 4595 AN: 10566

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.348 AC: 23673 AN: 67952

Other (OTH) AF: 0.423 AC: 894 AN: 2114

Alfa AF: 0.373 Hom.: 1349

Bravo AF: 0.409

Asia WGS AF: 0.551 AC: 1916 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	20
DANN	Benign	0.51
PhyloP100		0.17
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.56		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.56		Position offset: 3

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

Other links and lift over

dbSNP: rs7410608; hg19: chr22-50858813;