22-50415888-T-C

Position:

• chr22-50415888-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001242898.2(PPP6R2):​c.553-204T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.385 in 152,082 control chromosomes in the GnomAD database, including 11,716 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 0.39 (11716 hom., cov: 32)
• Consequence: PPP6R2 NM_001242898.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.483

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R2	NM_001242898.2	c.553-204T>C		intron_variant		ENST00000612753.5	NP_001229827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R2	ENST00000612753.5	c.553-204T>C		intron_variant		2	NM_001242898.2	ENSP00000478417.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58512 AN: 151964 Hom.: 11709 Cov.: 32

Gnomad AFR AF: 0.424

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.669

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.385 AC: 58563 AN: 152082 Hom.: 11716 Cov.: 32 AF XY: 0.392 AC XY: 29119 AN XY: 74344

Gnomad4 AFR AF: 0.424

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.397

Alfa AF: 0.346 Hom.: 2218

Bravo AF: 0.392

Asia WGS AF: 0.475 AC: 1654 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.2
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs6520165; hg19: chr22-50854317;