rs752726063

Variant names:

• chr14-56118668-C-A
• rs752726063
• NM_021255.3:c.8C>A

Your query was ambiguous. Multiple possible variants found:

• chr14-56118668-C-A
• chr14-56118668-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021255.3(PELI2):​c.8C>A​(p.Ser3Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000000759 in 1,317,256 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S3F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: PELI2 NM_021255.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.20

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27560636).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PELI2	NM_021255.3	c.8C>A	p.Ser3Tyr	missense_variant	Exon 1 of 6	ENST00000267460.9	NP_067078.1
PELI2	XM_005267890.6	c.8C>A	p.Ser3Tyr	missense_variant	Exon 1 of 6		XP_005267947.1
PELI2	XM_011536990.3	c.-347C>A		5_prime_UTR_variant	Exon 1 of 7		XP_011535292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PELI2	ENST00000267460.9	c.8C>A	p.Ser3Tyr	missense_variant	Exon 1 of 6	1	NM_021255.3	ENSP00000267460.4
PELI2	ENST00000705193.1	c.179C>A	p.Ser60Tyr	missense_variant	Exon 1 of 6			ENSP00000516089.1
PELI2	ENST00000559044.5	c.-224+588C>A		intron_variant	Intron 1 of 4	4		ENSP00000452666.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.59e-7 AC: 1 AN: 1317256 Hom.: 0 Cov.: 30 AF XY: 0.00000153 AC XY: 1 AN XY: 652168

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000865 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.052	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.65	T
M_CAP	Pathogenic	0.93	D
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.077
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.62	P
Vest4		0.24
MutPred		0.28		Loss of glycosylation at S3 (P = 0.0135);
MVP		0.17
MPC		1.6
ClinPred		0.98	D
GERP RS		3.5
Varity_R		0.39
gMVP		0.43

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: rs752726063; hg19: chr14-56585386;