22-50394061-G-T

Position:

• chr22-50394061-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001242898.2(PPP6R2):​c.153G>T​(p.Gln51His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP6R2 NM_001242898.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.239

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14655843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R2	NM_001242898.2	c.153G>T	p.Gln51His	missense_variant	3/24	ENST00000612753.5	NP_001229827.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R2	ENST00000612753.5	c.153G>T	p.Gln51His	missense_variant	3/24	2	NM_001242898.2	ENSP00000478417.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 20, 2024

The c.153G>T (p.Q51H) alteration is located in exon 3 (coding exon 1) of the PPP6R2 gene. This alteration results from a G to T substitution at nucleotide position 153, causing the glutamine (Q) at amino acid position 51 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	.;.;.;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.56	D
LIST_S2	Uncertain	0.93	D;D;D;D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L;L;L;L;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-2.1	N;.;N;N;N
REVEL	Benign	0.089
Sift	Uncertain	0.0090	D;.;D;D;D
Sift4G	Uncertain	0.021	D;D;D;D;D
Polyphen		0.71	P;P;P;P;P
Vest4		0.37
MutPred		0.37		Gain of catalytic residue at Q51 (P = 0.0145);Gain of catalytic residue at Q51 (P = 0.0145);Gain of catalytic residue at Q51 (P = 0.0145);Gain of catalytic residue at Q51 (P = 0.0145);Gain of catalytic residue at Q51 (P = 0.0145);
MVP		0.068
MPC		1.0
ClinPred		0.71	D
GERP RS		-0.49
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.091
gMVP		0.13

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-50832490;