chr8-89790263-A-G

Position:

• chr8-89790263-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003821.6(RIPK2):​c.1470A>G​(p.Leu490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,614,028 control chromosomes in the GnomAD database, including 1,553 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 0.058 (778 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (775 hom.)
• Consequence: RIPK2 NM_003821.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=-0.096 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1470A>G	p.Leu490=	synonymous_variant	11/11	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.1059A>G	p.Leu353=	synonymous_variant	10/10		NP_001362289.1
RIPK2	XM_011517357.3	c.957A>G	p.Leu319=	synonymous_variant	9/9		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1470A>G	p.Leu490=	synonymous_variant	11/11	1	NM_003821.6	ENSP00000220751	P1
RIPK2	ENST00000522965.1	c.*1109A>G		3_prime_UTR_variant, NMD_transcript_variant	10/10	1		ENSP00000429271

Frequencies

GnomAD3 genomes AF: 0.0577 AC: 8769 AN: 152080 Hom.: 771 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0253

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.0673

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0464

GnomAD3 exomes AF: 0.0208 AC: 5232 AN: 251104 Hom.: 388 AF XY: 0.0166 AC XY: 2246 AN XY: 135692

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0112

Gnomad ASJ exome AF: 0.00655

Gnomad EAS exome AF: 0.0608

Gnomad SAS exome AF: 0.00853

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00119

Gnomad OTH exome AF: 0.0118

GnomAD4 exome AF: 0.00827 AC: 12088 AN: 1461830 Hom.: 775 Cov.: 31 AF XY: 0.00782 AC XY: 5686 AN XY: 727228

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.00719

Gnomad4 EAS exome AF: 0.0510

Gnomad4 SAS exome AF: 0.00953

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.000690

Gnomad4 OTH exome AF: 0.0195

GnomAD4 genome AF: 0.0578 AC: 8794 AN: 152198 Hom.: 778 Cov.: 32 AF XY: 0.0562 AC XY: 4180 AN XY: 74414

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0253

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.0669

Gnomad4 SAS AF: 0.0164

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00156

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0122 Hom.: 289

Bravo AF: 0.0658

Asia WGS AF: 0.0590 AC: 205 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	6.0
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs16900617; hg19: chr8-90802491;