8-89784141-TAAA-T

Variant names:

• chr8-89784141-TAAA-T
• rs71268283
• NM_003821.6:c.1029+23_1029+25delAAA

Variant summary

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

The ENST00000220751.5(RIPK2):​c.1029+3_1029+5delAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 546,772 control chromosomes in the GnomAD database, including 7,113 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.37 (5666 hom., cov: 0)
  • Exomes 𝑓: 0.23 (1447 hom.)
• Consequence: RIPK2 ENST00000220751.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.769

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-89784141-TAAA-T is Benign according to our data. Variant chr8-89784141-TAAA-T is described in ClinVar as [Benign]. Clinvar id is 403380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+23_1029+25delAAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+23_618+25delAAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+23_516+25delAAA		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+5delAAA		splice_region_variant, intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+3_*668+5delAAA		splice_region_variant, intron_variant	Intron 7 of 9	1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.368 AC: 35513 AN: 96464 Hom.: 5668 Cov.: 0

Gnomad AFR AF: 0.231

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.381

GnomAD2 exomes AF: 0.0786 AC: 2247 AN: 28604 AF XY: 0.0737

Gnomad AFR exome AF: 0.0861

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.0596

Gnomad EAS exome AF: 0.104

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0738

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.230 AC: 103588 AN: 450302 Hom.: 1447 AF XY: 0.226 AC XY: 52857 AN XY: 233950

Gnomad4 AFR exome AF: 0.154 AC: 1417 AN: 9230

Gnomad4 AMR exome AF: 0.169 AC: 1811 AN: 10736

Gnomad4 ASJ exome AF: 0.162 AC: 1613 AN: 9966

Gnomad4 EAS exome AF: 0.0900 AC: 1770 AN: 19662

Gnomad4 SAS exome AF: 0.138 AC: 3478 AN: 25156

Gnomad4 FIN exome AF: 0.193 AC: 5363 AN: 27722

Gnomad4 NFE exome AF: 0.256 AC: 83110 AN: 324510

Gnomad4 Remaining exome AF: 0.215 AC: 4655 AN: 21678

GnomAD4 genome AF: 0.368 AC: 35504 AN: 96470 Hom.: 5666 Cov.: 0 AF XY: 0.366 AC XY: 16079 AN XY: 43924

Gnomad4 AFR AF: 0.230 AC: 0.230198 AN: 0.230198

Gnomad4 AMR AF: 0.391 AC: 0.390519 AN: 0.390519

Gnomad4 ASJ AF: 0.314 AC: 0.314029 AN: 0.314029

Gnomad4 EAS AF: 0.0682 AC: 0.0681658 AN: 0.0681658

Gnomad4 SAS AF: 0.280 AC: 0.280197 AN: 0.280197

Gnomad4 FIN AF: 0.570 AC: 0.569635 AN: 0.569635

Gnomad4 NFE AF: 0.439 AC: 0.439413 AN: 0.439413

Gnomad4 OTH AF: 0.381 AC: 0.380727 AN: 0.380727

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV55132790; COSMIC: COSV55132790;