16-71649182-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015020.3(PHLPP2):​c.3680A>G​(p.Gln1227Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

PHLPP2
NM_015020.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.73
Variant links:
Genes affected
PHLPP2 (HGNC:29149): (PH domain and leucine rich repeat protein phosphatase 2) Predicted to enable protein serine/threonine phosphatase activity. Predicted to be involved in signal transduction. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.15491706).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PHLPP2NM_015020.3 linkuse as main transcriptc.3680A>G p.Gln1227Arg missense_variant 19/19 ENST00000568954.5
PHLPP2NM_001289003.1 linkuse as main transcriptc.3479A>G p.Gln1160Arg missense_variant 18/18

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PHLPP2ENST00000568954.5 linkuse as main transcriptc.3680A>G p.Gln1227Arg missense_variant 19/191 NM_015020.3 P2Q6ZVD8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 27, 2024The c.3680A>G (p.Q1227R) alteration is located in exon 18 (coding exon 18) of the PHLPP2 gene. This alteration results from a A to G substitution at nucleotide position 3680, causing the glutamine (Q) at amino acid position 1227 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
0.091
BayesDel_addAF
Benign
-0.13
T
BayesDel_noAF
Benign
-0.42
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.011
T;.;T
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.82
T;T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.15
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L;.;.
MutationTaster
Benign
0.98
D;D;D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.65
N;N;N
REVEL
Benign
0.10
Sift
Benign
0.40
T;T;T
Sift4G
Benign
0.58
T;T;T
Polyphen
0.58
P;P;.
Vest4
0.082
MutPred
0.13
Loss of ubiquitination at K1228 (P = 0.0107);.;.;
MVP
0.51
MPC
0.10
ClinPred
0.58
D
GERP RS
6.2
Varity_R
0.13
gMVP
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2044675544; hg19: chr16-71683085; API