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 NM_003821.6(RIPK2):c.1029+24_1029+25dupAA variant causes a 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
NM_003821.6 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RIPK2	NM_003821.6 link	c.1029+24_1029+25dupAA	intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1 link	c.618+24_618+25dupAA	intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3 link	c.516+24_516+25dupAA	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 link	c.1029+24_1029+25dupAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

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 v4.3

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

Publications

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8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

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