8-89767579-A-G

Position:

• chr8-89767579-A-G

Variant summary

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

The NM_003821.6(RIPK2):​c.483+2083A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 151,506 control chromosomes in the GnomAD database, including 34,594 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.66 (34594 hom., cov: 31)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.350

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.483+2083A>G		intron_variant		ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.72+2083A>G		intron_variant			NP_001362289.1
RIPK2	XM_011517357.3	c.-31+470A>G		intron_variant			XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.483+2083A>G		intron_variant		1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*122+2083A>G		intron_variant		1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.658 AC: 99567 AN: 151388 Hom.: 34541 Cov.: 31

Gnomad AFR AF: 0.891

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.639

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

GnomAD4 genome AF: 0.658 AC: 99676 AN: 151506 Hom.: 34594 Cov.: 31 AF XY: 0.653 AC XY: 48348 AN XY: 74034

Gnomad4 AFR AF: 0.891

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.437

Gnomad4 EAS AF: 0.529

Gnomad4 SAS AF: 0.445

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.587

Gnomad4 OTH AF: 0.637

Alfa AF: 0.588 Hom.: 12198

Bravo AF: 0.663

Asia WGS AF: 0.519 AC: 1803 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.70

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: rs39503; hg19: chr8-90779807;