dbSNP rs16900617: RIPK2:p.Leu490Leu (chr8-89790263-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003821.6(RIPK2):c.1470A>G(p.Leu490Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0129 in 1,614,028 control chromosomes in the GnomAD database, including 1,553 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.058 ( 778 hom., cov: 32)

Exomes 𝑓: 0.0083 ( 775 hom. )

Consequence

RIPK2
NM_003821.6 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

Publications

11 publications found

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:

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

PARAIL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP7

Synonymous conserved (PhyloP=-0.096 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6 link	c.1470A>G	p.Leu490Leu	synonymous_variant	Exon 11 of 11	ENST00000220751.5	NP_003812.1	O43353-1A0A0S2Z4Z8
RIPK2	NM_001375360.1 link	c.1059A>G	p.Leu353Leu	synonymous_variant	Exon 10 of 10		NP_001362289.1
RIPK2	XM_011517357.3 link	c.957A>G	p.Leu319Leu	synonymous_variant	Exon 9 of 9		XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5 link	c.1470A>G	p.Leu490Leu	synonymous_variant	Exon 11 of 11	1	NM_003821.6	ENSP00000220751.4		O43353-1

Frequencies

GnomAD3 genomes

AF:

0.0577

AC:

8769

AN:

152080

Hom.:

771

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0253

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0673

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.00154

Gnomad OTH

AF:

0.0464

GnomAD2 exomes

AF:

0.0208

AC:

5232

AN:

251104

AF XY:

0.0166

show subpopulations

Gnomad AFR exome

AF:

0.196

Gnomad AMR exome

AF:

0.0112

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.0608

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.0118

GnomAD4 exome

AF:

0.00827

AC:

12088

AN:

1461830

Hom.:

775

Cov.:

AF XY:

0.00782

AC XY:

5686

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.194

AC:

6487

AN:

33474

American (AMR)

AF:

0.0118

AC:

529

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00719

AC:

188

AN:

26134

East Asian (EAS)

AF:

0.0510

AC:

2025

AN:

39692

South Asian (SAS)

AF:

0.00953

AC:

822

AN:

86258

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.0158

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000690

AC:

767

AN:

1111974

Other (OTH)

AF:

0.0195

AC:

1177

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

629

1258

1887

2516

3145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0578

AC:

8794

AN:

152198

Hom.:

778

Cov.:

AF XY:

0.0562

AC XY:

4180

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.187

AC:

7741

AN:

41464

American (AMR)

AF:

0.0253

AC:

386

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00778

AC:

AN:

3472

East Asian (EAS)

AF:

0.0669

AC:

346

AN:

5172

South Asian (SAS)

AF:

0.0164

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00156

AC:

106

AN:

68032

Other (OTH)

AF:

0.0478

AC:

101

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

376

752

1128

1504

1880

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0223

Hom.:

876

Bravo

AF:

0.0658

Asia WGS

AF:

0.0590

AC:

205

AN:

3478

EpiCase

AF:

0.00120

EpiControl

AF:

0.00101

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

6.0

(source)

DANN

Benign

0.83

PhyloP100

-0.096

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over