Genetic Variant RIPK2:c.1029+25delA (chr8-89784141-TA-T) – 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+3delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 424 hom., cov: 0)

Exomes 𝑓: 0.066 ( 9 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 (EAS) allele frequency at 95% confidence interval = 0.261 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+25delA		intron	N/A	NP_003812.1	O43353-1
	RIPK2	NM_001375360.1		c.618+25delA		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+3delA	splice_region intron	N/A	ENSP00000220751.4	O43353-1
RIPK2	ENST00000522965.1	TSL:1	n.*668+3delA	splice_region intron	N/A	ENSP00000429271.1	E7ERW9
RIPK2	ENST00000929530.1		c.1089+3delA	splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes

AF:

0.0984

AC:

9524

AN:

96758

Hom.:

426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.187

Gnomad AMI

AF:

0.00694

Gnomad AMR

AF:

0.0652

Gnomad ASJ

AF:

0.0401

Gnomad EAS

AF:

0.277

Gnomad SAS

AF:

0.150

Gnomad FIN

AF:

0.0803

Gnomad MID

AF:

0.0856

Gnomad NFE

AF:

0.0576

Gnomad OTH

AF:

0.0828

GnomAD4 exome

AF:

0.0656

AC:

29599

AN:

451060

Hom.:

Cov.:

AF XY:

0.0661

AC XY:

15516

AN XY:

234726

show subpopulations

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

African (AFR)

AF:

0.127

AC:

1175

AN:

9266

American (AMR)

AF:

0.0702

AC:

754

AN:

10748

Ashkenazi Jewish (ASJ)

AF:

0.0753

AC:

752

AN:

9988

East Asian (EAS)

AF:

0.169

AC:

3405

AN:

20134

South Asian (SAS)

AF:

0.0786

AC:

1993

AN:

25350

European-Finnish (FIN)

AF:

0.0487

AC:

1355

AN:

27838

Middle Eastern (MID)

AF:

0.0747

AC:

122

AN:

1634

European-Non Finnish (NFE)

AF:

0.0567

AC:

18400

AN:

324330

Other (OTH)

AF:

0.0755

AC:

1643

AN:

21772

⚠️ 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: 0.339

Heterozygous variant carriers

1903

3807

5710

7614

9517

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

418

836

1254

1672

2090

<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:

0.0984

AC:

9518

AN:

96766

Hom.:

424

Cov.:

AF XY:

0.102

AC XY:

4511

AN XY:

44062

show subpopulations

African (AFR)

AF:

0.187

AC:

4364

AN:

23334

American (AMR)

AF:

0.0651

AC:

580

AN:

8908

Ashkenazi Jewish (ASJ)

AF:

0.0401

AC:

112

AN:

2790

East Asian (EAS)

AF:

0.277

AC:

786

AN:

2836

South Asian (SAS)

AF:

0.150

AC:

363

AN:

2428

European-Finnish (FIN)

AF:

0.0803

AC:

209

AN:

2604

Middle Eastern (MID)

AF:

0.0777

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0576

AC:

2977

AN:

51650

Other (OTH)

AF:

0.0822

AC:

106

AN:

1290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

308

616

923

1231

1539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

216

324

432

540

<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

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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8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

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