chr2-169701461-C-G

Position:

• chr2-169701461-C-G

Variant summary

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

The ENST00000359744.8(PHOSPHO2):​c.490C>G​(p.Gln164Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHOSPHO2 ENST00000359744.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.08

Genes affected

PHOSPHO2 (HGNC:28316): (phosphatase, orphan 2) Predicted to enable phosphatase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

PHOSPHO2-KLHL23 (HGNC:):

KLHL23 (HGNC:27506): (kelch like family member 23)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.490C>G	p.Gln164Glu	missense_variant	4/4	ENST00000359744.8	NP_001008489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOSPHO2	ENST00000359744.8	c.490C>G	p.Gln164Glu	missense_variant	4/4	1	NM_001008489.4	ENSP00000352782.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Jun 27, 2022

The c.490C>G (p.Q164E) alteration is located in exon 4 (coding exon 1) of the PHOSPHO2 gene. This alteration results from a C to G substitution at nucleotide position 490, causing the glutamine (Q) at amino acid position 164 to be replaced by a glutamic acid (E). 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	0.13
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;T;T
Eigen	Uncertain	0.50
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	.;.;T;.
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.49	T;T;T;T
MetaSVM	Benign	-0.77	T
MutationAssessor	Pathogenic	2.9	M;M;M;M
MutationTaster	Benign	0.99	D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	.;.;.;N
REVEL	Uncertain	0.33
Sift	Uncertain	0.0090	.;.;.;D
Sift4G	Uncertain	0.022	D;D;D;D
Polyphen		0.91	P;P;P;P
Vest4		0.35
MutPred		0.72		Gain of ubiquitination at K163 (P = 0.1295);Gain of ubiquitination at K163 (P = 0.1295);Gain of ubiquitination at K163 (P = 0.1295);Gain of ubiquitination at K163 (P = 0.1295);
MVP		0.067
MPC		0.29
ClinPred		0.90	D
GERP RS		6.1
Varity_R		0.20
gMVP		0.68

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: chr2-170557971;