14-56118686-A-C

Variant names:

• chr14-56118686-A-C
• rs756865019
• NM_021255.3:c.26A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021255.3(PELI2):​c.26A>C​(p.His9Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H9R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PELI2 NM_021255.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.565
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0988535).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021255.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI2	NM_021255.3	MANE Select	c.26A>C	p.His9Pro	missense	Exon 1 of 6	NP_067078.1	Q9HAT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PELI2	ENST00000267460.9	TSL:1 MANE Select	c.26A>C	p.His9Pro	missense	Exon 1 of 6	ENSP00000267460.4	Q9HAT8
	PELI2	ENST00000705193.1		c.197A>C	p.His66Pro	missense	Exon 1 of 6	ENSP00000516089.1	A0A994J4T1
	PELI2	ENST00000559044.5	TSL:4	c.-224+606A>C		intron	N/A	ENSP00000452666.1	H0YK56

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.050
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.71
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.27	N
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.51	D
MetaRNN	Benign	0.099	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		0.56
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.065
Sift	Benign	0.36	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.39		Gain of catalytic residue at H9 (P = 0.0067)
MVP		0.082
MPC		0.75
ClinPred		0.67	D
GERP RS		-3.5
PromoterAI		-0.095	Neutral
Varity_R		0.073
gMVP		0.27
Mutation Taster		=78/22	polymorphism

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

Other links and lift over

dbSNP: rs756865019; hg19: chr14-56585404; COSMIC: COSV105082979; COSMIC: COSV105082979;