2-169701021-A-T

Variant names:

• chr2-169701021-A-T
• rs747218148
• NM_001008489.4:c.50A>T

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.50A>T​(p.Asn17Ile) variant causes a missense change involving the alteration of a conserved nucleotide. 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. N17S) 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: 7.82
• 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, 0.89

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.50A>T	p.Asn17Ile	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.50A>T	p.Asn17Ile	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	Pathogenic	0.85
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;T;T;.;.;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	.;.;D;.;D;D;D
M_CAP	Uncertain	0.16	D
MetaRNN	Pathogenic	0.89	D;D;D;D;D;D;D
MetaSVM	Uncertain	-0.22	T
MutationAssessor	Pathogenic	3.3	M;M;M;M;.;.;.
PhyloP100		7.8
PrimateAI	Uncertain	0.66	T
PROVEAN	Pathogenic	-7.7	.;.;.;D;D;D;D
REVEL	Pathogenic	0.72
Sift	Uncertain	0.0010	.;.;.;D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	D;D;D;D;.;.;.
Vest4		0.93
MutPred		0.70		Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);Loss of solvent accessibility (P = 0.0509);
MVP		0.22
MPC		0.52
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.88
gMVP		0.90
Mutation Taster		=17/83	disease causing

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: rs747218148; hg19: chr2-170557531;