14-56296737-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_021255.3(PELI2):c.834C>T(p.Asn278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,614,108 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (45 hom.)
• Consequence: PELI2 NM_021255.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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]

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 14-56296737-C-T is Benign according to our data. Variant chr14-56296737-C-T is described in ClinVar as [Benign]. Clinvar id is 777693.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.18 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PELI2	NM_021255.3	c.834C>T	p.Asn278=	synonymous_variant	6/6	ENST00000267460.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PELI2	ENST00000267460.9	c.834C>T	p.Asn278=	synonymous_variant	6/6	1	NM_021255.3	P1
PELI2	ENST00000705193.1	c.1005C>T	p.Asn335=	synonymous_variant	6/6

Frequencies

GnomAD3 genomes AF: 0.00492 AC: 749 AN: 152184 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00751

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00463 AC: 1161 AN: 250580 Hom.: 4 AF XY: 0.00478 AC XY: 648 AN XY: 135446

Gnomad AFR exome AF: 0.00160

Gnomad AMR exome AF: 0.00529

Gnomad ASJ exome AF: 0.00507

Gnomad EAS exome AF: 0.0000545

Gnomad SAS exome AF: 0.00121

Gnomad FIN exome AF: 0.00199

Gnomad NFE exome AF: 0.00697

Gnomad OTH exome AF: 0.00523

GnomAD4 exome AF: 0.00631 AC: 9224 AN: 1461806 Hom.: 45 Cov.: 32 AF XY: 0.00623 AC XY: 4529 AN XY: 727208

Gnomad4 AFR exome AF: 0.00125

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.00482

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000765

Gnomad4 FIN exome AF: 0.00199

Gnomad4 NFE exome AF: 0.00745

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome AF: 0.00492 AC: 749 AN: 152302 Hom.: 6 Cov.: 32 AF XY: 0.00449 AC XY: 334 AN XY: 74468

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.00179

Gnomad4 NFE AF: 0.00751

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00615 Hom.: 2

Bravo AF: 0.00490

EpiCase AF: 0.00654

EpiControl AF: 0.00747

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
Cadd	Benign	0.35
Dann	Benign	0.64

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

Other links and lift over

dbSNP: rs140013898; hg19: chr14-56763455; COSMIC: COSV99953940;