8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAA

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

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
• Publications: 0 publications found

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]

PARAIL (HGNC:55545): (palmitic acid regulated anti-inflammatory lncRNA)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 485 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000220751.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	NM_003821.6	MANE Select	c.1029+24_1029+25delAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+24_618+25delAA		intron	N/A	NP_001362289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+3_1029+4delAA		splice_region intron	N/A	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*668+3_*668+4delAA		splice_region intron	N/A	ENSP00000429271.1
	RIPK2	ENST00000929530.1		c.1089+3_1089+4delAA		splice_region intron	N/A	ENSP00000599589.1

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

GnomAD2 exomes AF: 0.0371 AC: 1060 AN: 28604 AF XY: 0.0358

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 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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.108 AC: 994 AN: 9228

American (AMR) AF: 0.0695 AC: 745 AN: 10720

Ashkenazi Jewish (ASJ) AF: 0.0661 AC: 654 AN: 9890

East Asian (EAS) AF: 0.128 AC: 2512 AN: 19558

South Asian (SAS) AF: 0.0743 AC: 1869 AN: 25154

European-Finnish (FIN) AF: 0.0480 AC: 1334 AN: 27802

Middle Eastern (MID) AF: 0.0766 AC: 125 AN: 1632

European-Non Finnish (NFE) AF: 0.0590 AC: 19094 AN: 323822

Other (OTH) AF: 0.0728 AC: 1576 AN: 21650

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00345 AC: 81 AN: 23464

American (AMR) AF: 0.00404 AC: 36 AN: 8916

Ashkenazi Jewish (ASJ) AF: 0.00823 AC: 23 AN: 2796

East Asian (EAS) AF: 0.00175 AC: 5 AN: 2856

South Asian (SAS) AF: 0.00450 AC: 11 AN: 2446

European-Finnish (FIN) AF: 0.00498 AC: 13 AN: 2608

Middle Eastern (MID) AF: 0.0146 AC: 3 AN: 206

European-Non Finnish (NFE) AF: 0.00559 AC: 289 AN: 51736

Other (OTH) AF: 0.00388 AC: 5 AN: 1290

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.039
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs71268283; hg19: chr8-90796369;