8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant names:

• chr8-89784141-TAA-T
• rs71268283
• NM_003821.6:c.1029+24_1029+25delAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000220751.5(RIPK2):​c.1029+3_1029+4delAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0538 in 546,494 control chromosomes in the GnomAD database, including 40 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0050 (0 hom., cov: 0)
  • Exomes 𝑓: 0.064 (40 hom.)
• Consequence: RIPK2 ENST00000220751.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+24_1029+25delAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+24_618+25delAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+24_516+25delAA		intron_variant	Intron 6 of 8		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+3_1029+4delAA		splice_region_variant, intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+3_*668+4delAA		splice_region_variant, intron_variant	Intron 7 of 9	1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.00498 AC: 483 AN: 97030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00337

Gnomad AMI AF: 0.0264

Gnomad AMR AF: 0.00404

Gnomad ASJ AF: 0.00823

Gnomad EAS AF: 0.00175

Gnomad SAS AF: 0.00448

Gnomad FIN AF: 0.00498

Gnomad MID AF: 0.0135

Gnomad NFE AF: 0.00559

Gnomad OTH AF: 0.00391

GnomAD3 exomes AF: 0.0371 AC: 1060 AN: 28604 Hom.: 0 AF XY: 0.0358 AC XY: 545 AN XY: 15204

Gnomad AFR exome AF: 0.0813

Gnomad AMR exome AF: 0.0615

Gnomad ASJ exome AF: 0.0356

Gnomad EAS exome AF: 0.128

Gnomad SAS exome AF: 0.0478

Gnomad FIN exome AF: 0.00838

Gnomad NFE exome AF: 0.0213

Gnomad OTH exome AF: 0.0517

GnomAD4 exome AF: 0.0643 AC: 28903 AN: 449456 Hom.: 40 AF XY: 0.0641 AC XY: 14978 AN XY: 233696

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.0695

Gnomad4 ASJ exome AF: 0.0661

Gnomad4 EAS exome AF: 0.128

Gnomad4 SAS exome AF: 0.0743

Gnomad4 FIN exome AF: 0.0480

Gnomad4 NFE exome AF: 0.0590

Gnomad4 OTH exome AF: 0.0728

GnomAD4 genome AF: 0.00500 AC: 485 AN: 97038 Hom.: 0 Cov.: 0 AF XY: 0.00489 AC XY: 216 AN XY: 44192

Gnomad4 AFR AF: 0.00345

Gnomad4 AMR AF: 0.00404

Gnomad4 ASJ AF: 0.00823

Gnomad4 EAS AF: 0.00175

Gnomad4 SAS AF: 0.00450

Gnomad4 FIN AF: 0.00498

Gnomad4 NFE AF: 0.00559

Gnomad4 OTH AF: 0.00388

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs71268283; hg19: chr8-90796369;