rs369192314

Variant names:

• chr2-169701284-A-C
• rs369192314
• NM_001008489.4:c.313A>C

Your query was ambiguous. Multiple possible variants found:

• chr2-169701284-A-C
• chr2-169701284-A-G
• chr2-169701284-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001008489.4(PHOSPHO2):​c.313A>C​(p.Ile105Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PHOSPHO2 NM_001008489.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.86

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.833

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.313A>C	p.Ile105Leu	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.313A>C	p.Ile105Leu	missense_variant	Exon 4 of 4	1	NM_001008489.4	ENSP00000352782.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000400 AC: 1 AN: 250248 Hom.: 0 AF XY: 0.00000739 AC XY: 1 AN XY: 135368

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461040 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 726750

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.074	T;T;T;T;.
Eigen	Pathogenic	0.89
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.81	.;.;T;.;T
M_CAP	Benign	0.053	D
MetaRNN	Pathogenic	0.83	D;D;D;D;D
MetaSVM	Uncertain	-0.068	T
MutationAssessor	Pathogenic	3.1	M;M;M;M;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-2.0	.;.;.;N;N
REVEL	Uncertain	0.43
Sift	Uncertain	0.0080	.;.;.;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D
Polyphen		0.99	D;D;D;D;.
Vest4		0.76
MutPred		0.75		Gain of catalytic residue at I105 (P = 0.0029);Gain of catalytic residue at I105 (P = 0.0029);Gain of catalytic residue at I105 (P = 0.0029);Gain of catalytic residue at I105 (P = 0.0029);Gain of catalytic residue at I105 (P = 0.0029);
MVP		0.38
MPC		0.41
ClinPred		0.87	D
GERP RS		5.5
Varity_R		0.53
gMVP		0.84

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

LitVar

Other links and lift over

dbSNP: rs369192314; hg19: chr2-170557794;