Variant 6-143753894-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001100164.2(PHACTR2):c.436C>G(p.Gln146Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,450,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 6.9e-7 ( 0 hom. )

Consequence

PHACTR2
NM_001100164.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.65

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:

PHACTR2 (HGNC:):

PHACTR2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06012532).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR2	NM_001100164.2 linkuse as main transcript	c.436C>G	p.Gln146Glu	missense_variant	4/13	ENST00000440869.7	NP_001093634.1	O75167-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7 linkuse as main transcript	c.436C>G	p.Gln146Glu	missense_variant	4/13	2	NM_001100164.2	ENSP00000417038.2		O75167-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450520

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

721658

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

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.:

Bravo

AF:

0.00000378

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

Apr 25, 2022

The c.436C>G (p.Q146E) alteration is located in exon 4 (coding exon 4) of the PHACTR2 gene. This alteration results from a C to G substitution at nucleotide position 436, causing the glutamine (Q) at amino acid position 146 to be replaced by a glutamic acid (E). 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

0.061

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.0037

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

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.67

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

M_CAP

Benign

0.0044

MetaRNN

Benign

0.060

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

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.55

.;N;N;.;.;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

0.11

N;N;N;N;N;N;N

REVEL

Benign

0.060

Sift

Benign

0.38

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

Sift4G

Benign

1.0

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

Polyphen

0.0

.;B;B;B;B;.;.

Vest4

0.20

MutPred

0.13

.;Loss of loop (P = 0.0374);Loss of loop (P = 0.0374);.;.;.;.;

MVP

0.33

MPC

0.070

ClinPred

0.18

GERP RS

1.0

Varity_R

0.052

gMVP

0.089

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