2-169700976-A-G

Position:

• chr2-169700976-A-G

Variant summary

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

The NM_001008489.4(PHOSPHO2):​c.5A>G​(p.Lys2Arg) 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 NM_001008489.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.25

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.5A>G	p.Lys2Arg	missense_variant	4/4	ENST00000359744.8	NP_001008489.1
PHOSPHO2-KLHL23	NR_144936.2	n.358+3445A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOSPHO2	ENST00000359744.8	c.5A>G	p.Lys2Arg	missense_variant	4/4	1	NM_001008489.4	ENSP00000352782	P1

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

Dec 14, 2021

The c.5A>G (p.K2R) 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 5, causing the lysine (K) at amino acid position 2 to be replaced by an arginine (R). 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	0.087
BayesDel_addAF	Benign	-0.070	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;T;T;T;.;.;.
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.63	.;.;T;.;T;T;T
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.57	D;D;D;D;D;D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L;L;L;L;.;.;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.99	.;.;.;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.65	.;.;.;T;T;T;T
Sift4G	Benign	0.31	T;T;T;T;T;T;T
Polyphen		0.50	P;P;P;P;.;.;.
Vest4		0.59
MutPred		0.64		Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);Loss of ubiquitination at K2 (P = 0.0174);
MVP		0.39
MPC		0.14
ClinPred		0.82	D
GERP RS		4.9
Varity_R		0.15
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr2-170557486;