chr2-169701501-T-G

Variant names:

• chr2-169701501-T-G
• rs774495914
• NM_001008489.4:c.530T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001008489.4(PHOSPHO2):​c.530T>G​(p.Ile177Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I177T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHOSPHO2 NM_001008489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.11
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.530T>G	p.Ile177Ser	missense_variant	Exon 4 of 4	ENST00000359744.8	NP_001008489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHOSPHO2	ENST00000359744.8	c.530T>G	p.Ile177Ser	missense_variant	Exon 4 of 4	1	NM_001008489.4	ENSP00000352782.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;T;T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.86	.;.;D;.
M_CAP	Benign	0.066	D
MetaRNN	Pathogenic	0.91	D;D;D;D
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.7	M;M;M;M
PhyloP100		5.1
PrimateAI	Benign	0.37	T
PROVEAN	Pathogenic	-4.7	.;.;.;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0010	.;.;.;D
Sift4G	Uncertain	0.0030	D;D;D;D
Polyphen		0.92	P;P;P;P
Vest4		0.88
MutPred		0.80		Gain of glycosylation at I177 (P = 0.0604);Gain of glycosylation at I177 (P = 0.0604);Gain of glycosylation at I177 (P = 0.0604);Gain of glycosylation at I177 (P = 0.0604);
MVP		0.32
MPC		0.40
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.78
gMVP		0.85
Mutation Taster		=74/26	polymorphism

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

Other links and lift over

dbSNP: rs774495914; hg19: chr2-170558011;