Genetic Variant PELI2:p.Ser3Phe (chr14-56118668-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_021255.3(PELI2):c.8C>T(p.Ser3Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000038 in 1,317,254 control chromosomes in the GnomAD database, including 1 homozygotes. 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)

Exomes 𝑓: 0.0000038 ( 1 hom. )

Consequence

PELI2
NM_021255.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

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 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=0.24266249).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
PELI2	NM_021255.3 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 6	ENST00000267460.9	NP_067078.1
PELI2	XM_005267890.6 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 6		XP_005267947.1
PELI2	XM_011536990.3 link	c.-347C>T		5_prime_UTR_variant	Exon 1 of 7		XP_011535292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PELI2	ENST00000267460.9 link	c.8C>T	p.Ser3Phe	missense_variant	Exon 1 of 6	1	NM_021255.3	ENSP00000267460.4	Q9HAT8
PELI2	ENST00000705193.1 link	c.179C>T	p.Ser60Phe	missense_variant	Exon 1 of 6			ENSP00000516089.1	A0A994J4T1
PELI2	ENST00000559044.5 link	c.-224+588C>T		intron_variant	Intron 1 of 4	4		ENSP00000452666.1	H0YK56

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

123174

Hom.:

AF XY:

0.0000146

AC XY:

AN XY:

68506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000529

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000380

AC:

AN:

1317254

Hom.:

Cov.:

AF XY:

0.00000460

AC XY:

AN XY:

652166

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000141

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000193

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000865

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.8C>T (p.S3F) alteration is located in exon 1 (coding exon 1) of the PELI2 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a phenylalanine (F). 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

0.11

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

Eigen

Benign

0.051

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.93

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.8

REVEL

Benign

0.078

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.35

Vest4

0.23

MutPred

0.34

Gain of catalytic residue at S3 (P = 8e-04);

MVP

0.17

MPC

1.4

ClinPred

0.96

GERP RS

3.5

Varity_R

0.40

gMVP

0.42

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