Variant 8-89784141-TAAA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_003821.6(RIPK2):c.1029+23_1029+25del variant causes a splice donor 5th base, 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
NM_003821.6 splice_donor_5th_base, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.769

Variant links:

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]

RIPK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE
RIPK2	NM_003821.6 linkuse as main transcript	c.1029+23_1029+25del	splice_donor_5th_base_variant, intron_variant	ENST00000220751.5
RIPK2	NM_001375360.1 linkuse as main transcript	c.618+23_618+25del	splice_donor_5th_base_variant, intron_variant
RIPK2	XM_011517357.3 linkuse as main transcript	c.516+23_516+25del	splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RIPK2	ENST00000220751.5 linkuse as main transcript	c.1029+23_1029+25del		splice_donor_5th_base_variant, intron_variant		1	NM_003821.6	P1	O43353-1
RIPK2	ENST00000522965.1 linkuse as main transcript	c.668+23_668+25del		splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

35513

AN:

96464

Hom.:

5668

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0786

AC:

2247

AN:

28604

Hom.:

AF XY:

0.0737

AC XY:

1120

AN XY:

15204

show subpopulations

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 SAS exome

AF:

0.0759

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

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.169

Gnomad4 ASJ exome

AF:

0.162

Gnomad4 EAS exome

AF:

0.0900

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.193

Gnomad4 NFE exome

AF:

0.256

Gnomad4 OTH exome

AF:

0.215

GnomAD4 genome

AF:

0.368

AC:

35504

AN:

96470

Hom.:

5666

Cov.:

AF XY:

0.366

AC XY:

16079

AN XY:

43924

show subpopulations

Gnomad4 AFR

AF:

0.230

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.314

Gnomad4 EAS

AF:

0.0682

Gnomad4 SAS

AF:

0.280

Gnomad4 FIN

AF:

0.570

Gnomad4 NFE

AF:

0.439

Gnomad4 OTH

AF:

0.381

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over