Variant chr6-143765264-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001100164.2(PHACTR2):c.698G>T(p.Gly233Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,380 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PHACTR2
NM_001100164.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.02

Variant links:

Genes affected

PHACTR2 (HGNC:20956): (phosphatase and actin regulator 2) Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in plasma membrane and platelet alpha granule membrane. Implicated in Parkinson's disease and multiple sclerosis. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

PHACTR2 links:

Genome browser will be placed here

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=0.22126317).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100164.2 link	c.698G>T	p.Gly233Val	missense_variant	6/13	ENST00000440869.7	NP_001093634.1	O75167-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7 link	c.698G>T	p.Gly233Val	missense_variant	6/13	2	NM_001100164.2	ENSP00000417038.2		O75167-4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151996

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247390

Hom.:

AF XY:

0.00000744

AC XY:

AN XY:

134412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000561

Gnomad SAS 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:

6.86e-7

AC:

AN:

1458380

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725638

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151996

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74212

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000828

AC:

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 submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.698G>T (p.G233V) alteration is located in exon 6 (coding exon 6) of the PHACTR2 gene. This alteration results from a G to T substitution at nucleotide position 698, causing the glycine (G) at amino acid position 233 to be replaced by a valine (V). 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

0.098

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0077

.;T;.;.;.;T;T

Eigen

Uncertain

0.27

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.90

D;T;D;T;D;T;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.19

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L;.;.;.;.;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

N;N;N;N;N;D;N

REVEL

Benign

0.064

Sift

Pathogenic

0.0

D;T;D;T;D;D;D

Sift4G

Uncertain

0.012

D;T;D;T;D;D;D

Polyphen

0.88, 0.93, 0.96

.;P;P;D;P;.;.

Vest4

0.31

MutPred

0.21

.;Loss of relative solvent accessibility (P = 0.0071);.;.;.;.;.;

MVP

0.70

MPC

0.43

ClinPred

0.77

GERP RS

4.7

Varity_R

0.14

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over