Variant 2-131218415-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001083538.3(POTEE):c.13G>A(p.Val5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00642 in 1,612,858 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 5 hom., cov: 28)

Exomes 𝑓: 0.0066 ( 36 hom. )

Consequence

POTEE
NM_001083538.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.717

Variant links:

Genes affected

POTEE (HGNC:33895): (POTE ankyrin domain family member E) Involved in retina homeostasis and substantia nigra development. Located in blood microparticle and extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

POTEE links:

PLEKHB2 (HGNC:19236): (pleckstrin homology domain containing B2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity. Predicted to be involved in regulation of cell differentiation. Predicted to be located in recycling endosome membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PLEKHB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0044018924).

BP6

Variant 2-131218415-G-A is Benign according to our data. Variant chr2-131218415-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2651372.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
POTEE	NM_001083538.3 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	4/18	ENST00000683005.1
POTEE	XM_047444421.1 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	3/17
POTEE	XM_047444418.1 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POTEE	ENST00000683005.1 linkuse as main transcript	c.13G>A	p.Val5Ile	missense_variant	4/18		NM_001083538.3	P1	Q6S8J3-1

Frequencies

GnomAD3 genomes

AF:

0.00430

AC:

653

AN:

151710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000866

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00538

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00699

Gnomad OTH

AF:

0.00385

GnomAD3 exomes

AF:

0.00388

AC:

961

AN:

247468

Hom.:

AF XY:

0.00378

AC XY:

509

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.00113

Gnomad AMR exome

AF:

0.00250

Gnomad ASJ exome

AF:

0.000601

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.000948

Gnomad FIN exome

AF:

0.00498

Gnomad NFE exome

AF:

0.00621

Gnomad OTH exome

AF:

0.00334

GnomAD4 exome

AF:

0.00664

AC:

9701

AN:

1461032

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

4682

AN XY:

726834

show subpopulations

Gnomad4 AFR exome

AF:

0.000867

Gnomad4 AMR exome

AF:

0.00259

Gnomad4 ASJ exome

AF:

0.000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000986

Gnomad4 FIN exome

AF:

0.00541

Gnomad4 NFE exome

AF:

0.00802

Gnomad4 OTH exome

AF:

0.00413

GnomAD4 genome

AF:

0.00429

AC:

651

AN:

151826

Hom.:

Cov.:

AF XY:

0.00419

AC XY:

311

AN XY:

74210

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.00321

Gnomad4 ASJ

AF:

0.000866

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00538

Gnomad4 NFE

AF:

0.00696

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.00407

Hom.:

Bravo

AF:

0.00399

ExAC

AF:

0.00373

AC:

452

EpiCase

AF:

0.00502

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

POTEE: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.3

DANN

Benign

0.97

DEOGEN2

Benign

0.019

T;.;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.74

T;T;T

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0044

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

0.97

L;L;.

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.080

N;.;.

REVEL

Benign

0.017

Sift

Uncertain

0.0020

D;.;.

Sift4G

Uncertain

0.0040

D;D;D

Polyphen

0.27

B;.;.

Vest4

0.11

MVP

0.17

ClinPred

0.0040

Varity_R

0.18

gMVP

0.0075

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