Genetic Variant RIPK2:c.1029+24_1029+25dupAA (chr8-89784141-T-TAA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000220751.5(RIPK2):c.1029+2_1029+3insAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.028 ( 96 hom., cov: 0)

Exomes 𝑓: 0.012 ( 1 hom. )

Consequence

RIPK2
ENST00000220751.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.604

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0525 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+24_1029+25dupAA		intron	N/A	NP_003812.1	O43353-1
	RIPK2	NM_001375360.1		c.618+24_618+25dupAA		intron	N/A	NP_001362289.1	O43353-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+2_1029+3insAA	splice_region intron	N/A	ENSP00000220751.4	O43353-1
RIPK2	ENST00000522965.1	TSL:1	n.668+2_668+3insAA	splice_region intron	N/A	ENSP00000429271.1	E7ERW9
RIPK2	ENST00000929530.1		c.1089+2_1089+3insAA	splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

2711

AN:

96892

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.0307

Gnomad AMR

AF:

0.0181

Gnomad ASJ

AF:

0.0879

Gnomad EAS

AF:

0.00770

Gnomad SAS

AF:

0.0293

Gnomad FIN

AF:

0.00652

Gnomad MID

AF:

0.0182

Gnomad NFE

AF:

0.0164

Gnomad OTH

AF:

0.0282

GnomAD4 exome

AF:

0.0117

AC:

5341

AN:

457770

Hom.:

Cov.:

AF XY:

0.0122

AC XY:

2909

AN XY:

238220

show subpopulations

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

African (AFR)

AF:

0.0261

AC:

244

AN:

9342

American (AMR)

AF:

0.0151

AC:

165

AN:

10960

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

249

AN:

10084

East Asian (EAS)

AF:

0.0159

AC:

325

AN:

20402

South Asian (SAS)

AF:

0.0277

AC:

711

AN:

25702

European-Finnish (FIN)

AF:

0.00746

AC:

211

AN:

28298

Middle Eastern (MID)

AF:

0.0126

AC:

AN:

1670

European-Non Finnish (NFE)

AF:

0.00952

AC:

3134

AN:

329164

Other (OTH)

AF:

0.0127

AC:

281

AN:

22148

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.317

Heterozygous variant carriers

386

772

1158

1544

1930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<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:

0.0280

AC:

2715

AN:

96900

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

1258

AN XY:

44134

show subpopulations

African (AFR)

AF:

0.0549

AC:

1288

AN:

23440

American (AMR)

AF:

0.0181

AC:

161

AN:

8904

Ashkenazi Jewish (ASJ)

AF:

0.0879

AC:

245

AN:

2788

East Asian (EAS)

AF:

0.00771

AC:

AN:

2852

South Asian (SAS)

AF:

0.0295

AC:

AN:

2444

European-Finnish (FIN)

AF:

0.00652

AC:

AN:

2608

Middle Eastern (MID)

AF:

0.0196

AC:

AN:

204

European-Non Finnish (NFE)

AF:

0.0164

AC:

847

AN:

51656

Other (OTH)

AF:

0.0287

AC:

AN:

1288

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.517

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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.

Publications

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8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over