2-169701686-A-G

Position:

• chr2-169701686-A-G

Variant summary

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

The ENST00000359744.8(PHOSPHO2):​c.715A>G​(p.Ile239Val) 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. 15/21 in silico tools predict a benign outcome for this variant. 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: 1.53

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16785324).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.715A>G	p.Ile239Val	missense_variant	4/4	ENST00000359744.8	NP_001008489.1
PHOSPHO2-KLHL23	NR_144936.2	n.358+4155A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOSPHO2	ENST00000359744.8	c.715A>G	p.Ile239Val	missense_variant	4/4	1	NM_001008489.4	ENSP00000352782	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Mar 22, 2023

The c.715A>G (p.I239V) alteration is located in exon 4 (coding exon 1) of the PHOSPHO2 gene. This alteration results from a A to G substitution at nucleotide position 715, causing the isoleucine (I) at amino acid position 239 to be replaced by a valine (V). 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	0.080
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.014	T;T;T;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0067
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.40	.;.;T;.
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;L;L
MutationTaster	Benign	0.73	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.41	.;.;.;N
REVEL	Benign	0.059
Sift	Benign	0.27	.;.;.;T
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.10	B;B;B;B
Vest4		0.25
MutPred		0.69		Gain of methylation at K240 (P = 0.1249);Gain of methylation at K240 (P = 0.1249);Gain of methylation at K240 (P = 0.1249);Gain of methylation at K240 (P = 0.1249);
MVP		0.014
MPC		0.12
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.040
gMVP		0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr2-170558196;