8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

• chr8-89784141-T-TA
• rs71268283
• NM_003821.6:c.1029+25dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000220751.5(RIPK2):​c.1029+2_1029+3insA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (5283 hom., cov: 0)
  • Exomes 𝑓: 0.075 (11 hom.)
• Consequence: RIPK2 ENST00000220751.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.604
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-89784141-T-TA is Benign according to our data. Variant chr8-89784141-T-TA is described in ClinVar as Benign. ClinVar VariationId is 2867178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

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+25dupA		intron	N/A	NP_003812.1	O43353-1
	RIPK2	NM_001375360.1		c.618+25dupA		intron	N/A	NP_001362289.1	O43353-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+2_1029+3insA		splice_region intron	N/A	ENSP00000220751.4	O43353-1
	RIPK2	ENST00000522965.1	TSL:1	n.*668+2_*668+3insA		splice_region intron	N/A	ENSP00000429271.1	E7ERW9
	RIPK2	ENST00000929530.1		c.1089+2_1089+3insA		splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 31322 AN: 96572 Hom.: 5282 Cov.: 0

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.327

GnomAD2 exomes AF: 0.0323 AC: 925 AN: 28604 AF XY: 0.0305

Gnomad AFR exome AF: 0.0380

Gnomad AMR exome AF: 0.0782

Gnomad ASJ exome AF: 0.0489

Gnomad EAS exome AF: 0.0809

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.0215

Gnomad OTH exome AF: 0.0441

GnomAD4 exome AF: 0.0750 AC: 33709 AN: 449438 Hom.: 11 Cov.: 0 AF XY: 0.0754 AC XY: 17632 AN XY: 233904

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

African (AFR) AF: 0.0452 AC: 422 AN: 9328

American (AMR) AF: 0.0882 AC: 946 AN: 10730

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 1063 AN: 9932

East Asian (EAS) AF: 0.130 AC: 2591 AN: 19860

South Asian (SAS) AF: 0.104 AC: 2645 AN: 25466

European-Finnish (FIN) AF: 0.0538 AC: 1498 AN: 27842

Middle Eastern (MID) AF: 0.0704 AC: 115 AN: 1634

European-Non Finnish (NFE) AF: 0.0704 AC: 22727 AN: 322944

Other (OTH) AF: 0.0784 AC: 1702 AN: 21702

⚠️ 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: 0.324 AC: 31320 AN: 96586 Hom.: 5283 Cov.: 0 AF XY: 0.320 AC XY: 14085 AN XY: 43948

African (AFR) AF: 0.123 AC: 2889 AN: 23430

American (AMR) AF: 0.409 AC: 3603 AN: 8820

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1247 AN: 2784

East Asian (EAS) AF: 0.436 AC: 1244 AN: 2852

South Asian (SAS) AF: 0.452 AC: 1094 AN: 2422

European-Finnish (FIN) AF: 0.261 AC: 669 AN: 2564

Middle Eastern (MID) AF: 0.277 AC: 57 AN: 206

European-Non Finnish (NFE) AF: 0.383 AC: 19725 AN: 51510

Other (OTH) AF: 0.327 AC: 418 AN: 1278

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.60
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs71268283; hg19: chr8-90796369; COSMIC: COSV55131860; COSMIC: COSV55131860;