rs42490

chr8-89766285-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003821.6(RIPK2):c.483+789G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,632 control chromosomes in the GnomAD database, including 27,677 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain risk allele (no stars).

• Frequency: Genomes: 𝑓 0.60 (27677 hom., cov: 32)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Uncertain risk allele no assertion criteria provided O:1
• Conservation: PhyloP100: -0.275

Genes affected

RIPK2 (HGNC:10020): (receptor interacting serine/threonine kinase 2) This gene encodes a member of the receptor-interacting protein (RIP) family of serine/threonine protein kinases. The encoded protein contains a C-terminal caspase activation and recruitment domain (CARD), and is a component of signaling complexes in both the innate and adaptive immune pathways. It is a potent activator of NF-kappaB and inducer of apoptosis in response to various stimuli. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RIPK2	NM_003821.6	c.483+789G>A		intron_variant		ENST00000220751.5
RIPK2	NM_001375360.1	c.72+789G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK2	ENST00000220751.5	c.483+789G>A		intron_variant		1	NM_003821.6	P1
RIPK2	ENST00000522965.1	c.*122+789G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90629 AN: 151512 Hom.: 27640 Cov.: 32

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.450

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.429

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.662

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.592

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.598 AC: 90713 AN: 151632 Hom.: 27677 Cov.: 32 AF XY: 0.595 AC XY: 44080 AN XY: 74134

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.429

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.588

Alfa AF: 0.572 Hom.: 41641

Bravo AF: 0.595

Asia WGS AF: 0.460 AC: 1599 AN: 3476

ClinVar

Significance: Uncertain risk allele

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Leprosy, susceptibility to, 1 Other:1

Uncertain risk allele, no assertion criteria provided

case-control

Centro Dermatológico Federico Lleras Acosta, Hospital Universitario Centro Dermatológico Federico Lleras Acosta

Jun 10, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.025
Dann	Benign	0.35

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: rs42490; hg19: chr8-90778513;