8-89761018-G-A

Position:

• chr8-89761018-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.174-1811G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,154 control chromosomes in the GnomAD database, including 3,915 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 0.19 (3915 hom., cov: 32)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.483

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.174-1811G>A		intron_variant		ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.-85+2785G>A		intron_variant			NP_001362289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.174-1811G>A		intron_variant		1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.173+2785G>A		intron_variant		1		ENSP00000429271.1
RIPK2	ENST00000517696.1	n.*85+1572G>A		intron_variant		4		ENSP00000427736.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28307 AN: 152036 Hom.: 3895 Cov.: 32

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0876

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.186 AC: 28364 AN: 152154 Hom.: 3915 Cov.: 32 AF XY: 0.182 AC XY: 13526 AN XY: 74398

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.0702

Gnomad4 FIN AF: 0.0876

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.171

Alfa AF: 0.0861 Hom.: 171

Bravo AF: 0.200

Asia WGS AF: 0.113 AC: 393 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.3
DANN	Benign	0.72

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: rs10504881; hg19: chr8-90773246;