chr2-169701576-A-T

Variant names:

• chr2-169701576-A-T
• rs1478781213
• NM_001008489.4:c.605A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008489.4(PHOSPHO2):​c.605A>T​(p.Tyr202Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PHOSPHO2 NM_001008489.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16545358).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008489.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOSPHO2	NM_001008489.4	MANE Select	c.605A>T	p.Tyr202Phe	missense	Exon 4 of 4	NP_001008489.1	Q8TCD6
	PHOSPHO2	NM_001199285.2		c.605A>T	p.Tyr202Phe	missense	Exon 4 of 4	NP_001186214.1	Q8TCD6
	PHOSPHO2	NM_001199286.2		c.605A>T	p.Tyr202Phe	missense	Exon 4 of 4	NP_001186215.1	Q8TCD6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHOSPHO2	ENST00000359744.8	TSL:1 MANE Select	c.605A>T	p.Tyr202Phe	missense	Exon 4 of 4	ENSP00000352782.3	Q8TCD6
	PHOSPHO2	ENST00000616481.4	TSL:3	c.605A>T	p.Tyr202Phe	missense	Exon 5 of 5	ENSP00000481680.1	Q8TCD6
	PHOSPHO2	ENST00000616524.4	TSL:3	c.605A>T	p.Tyr202Phe	missense	Exon 4 of 4	ENSP00000481046.1	Q8TCD6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249566 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459864 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726288

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.00 AC: 0 AN: 86234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51542

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111938

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.039	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.073
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.82	L
PhyloP100		2.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.065
Sift	Benign	0.46	T
Sift4G	Benign	0.49	T
Polyphen		0.046	B
Vest4		0.32
MutPred		0.69		Loss of methylation at K206 (P = 0.0488)
MVP		0.030
MPC		0.12
ClinPred		0.17	T
GERP RS		3.4
Varity_R		0.091
gMVP		0.36
Mutation Taster		=92/8	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: rs1478781213; hg19: chr2-170558086;