Genetic Variant PELI2:p.Arg209His (chr14-56290386-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_021255.3(PELI2):c.626G>A(p.Arg209His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0104 in 1,613,652 control chromosomes in the GnomAD database, including 112 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 8 hom., cov: 32)

Exomes 𝑓: 0.011 ( 104 hom. )

Consequence

PELI2
NM_021255.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

PELI2 (HGNC:8828): (pellino E3 ubiquitin protein ligase family member 2) Predicted to enable protein-macromolecule adaptor activity and ubiquitin protein ligase activity. Acts upstream of or within positive regulation of MAPK cascade and positive regulation of protein phosphorylation. Predicted to be located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

PELI2 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=0.022110939).

BP6

Variant 14-56290386-G-A is Benign according to our data. Variant chr14-56290386-G-A is described in ClinVar as [Benign]. Clinvar id is 771903.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PELI2	NM_021255.3 link	c.626G>A	p.Arg209His	missense_variant	Exon 5 of 6	ENST00000267460.9	NP_067078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PELI2	ENST00000267460.9 link	c.626G>A	p.Arg209His	missense_variant	Exon 5 of 6	1	NM_021255.3	ENSP00000267460.4	Q9HAT8
PELI2	ENST00000705193.1 link	c.797G>A	p.Arg266His	missense_variant	Exon 5 of 6			ENSP00000516089.1	A0A994J4T1
PELI2	ENST00000559044.5 link	c.*42G>A		downstream_gene_variant		4		ENSP00000452666.1	H0YK56
PELI2	ENST00000561019.1 link	c.*93G>A		downstream_gene_variant		5		ENSP00000453988.1	H0YNF4

Frequencies

GnomAD3 genomes

AF:

0.00756

AC:

1150

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.0115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.00861

GnomAD3 exomes

AF:

0.00773

AC:

1940

AN:

251064

Hom.:

AF XY:

0.00786

AC XY:

1066

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.00185

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.0119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00209

Gnomad FIN exome

AF:

0.0115

Gnomad NFE exome

AF:

0.0122

Gnomad OTH exome

AF:

0.00752

GnomAD4 exome

AF:

0.0107

AC:

15569

AN:

1461384

Hom.:

104

Cov.:

AF XY:

0.0103

AC XY:

7490

AN XY:

727006

show subpopulations

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00168

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00204

Gnomad4 FIN exome

AF:

0.0123

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00817

GnomAD4 genome

AF:

0.00756

AC:

1151

AN:

152268

Hom.:

Cov.:

AF XY:

0.00756

AC XY:

563

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0115

Gnomad4 NFE

AF:

0.0121

Gnomad4 OTH

AF:

0.00852

Alfa

AF:

0.0105

Hom.:

Bravo

AF:

0.00649

TwinsUK

AF:

0.0121

AC:

ALSPAC

AF:

0.0125

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00834

AC:

1013

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0107

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 18, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.81

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.25

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.30

Eigen

Pathogenic

0.99

Eigen_PC

Pathogenic

0.96

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

MetaRNN

Benign

0.022

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.0

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.56

Sift

Benign

0.049

Sift4G

Uncertain

0.051

Polyphen

1.0

Vest4

0.87

MVP

0.64

MPC

1.5

ClinPred

0.052

GERP RS

5.8

Varity_R

0.33

gMVP

0.82

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