chr2-169701615-T-A

Position:

• chr2-169701615-T-A

Variant summary

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

The NM_001008489.4(PHOSPHO2):​c.644T>A​(p.Leu215His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PHOSPHO2 NM_001008489.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.977

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=0.15004519).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHOSPHO2	NM_001008489.4	c.644T>A	p.Leu215His	missense_variant	4/4	ENST00000359744.8	NP_001008489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHOSPHO2	ENST00000359744.8	c.644T>A	p.Leu215His	missense_variant	4/4	1	NM_001008489.4	ENSP00000352782.3

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

Jul 16, 2024

The c.644T>A (p.L215H) alteration is located in exon 4 (coding exon 1) of the PHOSPHO2 gene. This alteration results from a T to A substitution at nucleotide position 644, causing the leucine (L) at amino acid position 215 to be replaced by a histidine (H). 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	0.089
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.018	T;T;T;T
Eigen	Benign	-0.047
Eigen_PC	Benign	0.027
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.46	.;.;T;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.6	L;L;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.49	.;.;.;N
REVEL	Benign	0.13
Sift	Benign	0.17	.;.;.;T
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.47	P;P;P;P
Vest4		0.31
MutPred		0.44		Gain of disorder (P = 0.0203);Gain of disorder (P = 0.0203);Gain of disorder (P = 0.0203);Gain of disorder (P = 0.0203);
MVP		0.048
MPC		0.35
ClinPred		0.40	T
GERP RS		2.3
Varity_R		0.068
gMVP		0.36

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-170558125;