Genetic Variant RIPK2:c.1029+18_1029+25delAAAAAAAA (chr8-89784141-TAAAAAAAA-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000220751.5(RIPK2):c.1029+3_1029+10delAAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00187 in 556,984 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0022 ( 0 hom. )

Consequence

RIPK2
ENST00000220751.5 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.92

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 15 AD gene.

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+18_1029+25delAAAAAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+18_618+25delAAAAAAAA		intron	N/A	NP_001362289.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+3_1029+10delAAAAAAAA	splice_region intron	N/A	ENSP00000220751.4
RIPK2	ENST00000522965.1	TSL:1	n.668+3_668+10delAAAAAAAA	splice_region intron	N/A	ENSP00000429271.1
RIPK2	ENST00000929530.1		c.1089+3_1089+10delAAAAAAAA	splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

97064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000427

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00107

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00450

Gnomad NFE

AF:

0.000174

Gnomad OTH

AF:

0.000780

GnomAD4 exome

AF:

0.00223

AC:

1024

AN:

459912

Hom.:

AF XY:

0.00224

AC XY:

536

AN XY:

239288

show subpopulations

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

African (AFR)

AF:

0.00179

AC:

AN:

9510

American (AMR)

AF:

0.00291

AC:

AN:

11006

Ashkenazi Jewish (ASJ)

AF:

0.00254

AC:

AN:

10242

East Asian (EAS)

AF:

0.000145

AC:

AN:

20656

South Asian (SAS)

AF:

0.00143

AC:

AN:

25822

European-Finnish (FIN)

AF:

0.00162

AC:

AN:

28380

Middle Eastern (MID)

AF:

0.00238

AC:

AN:

1684

European-Non Finnish (NFE)

AF:

0.00245

AC:

809

AN:

330332

Other (OTH)

AF:

0.00224

AC:

AN:

22280

⚠️ 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: 0.276

Heterozygous variant carriers

100

200

301

401

501

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<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:

0.000155

AC:

AN:

97072

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

44206

show subpopulations

African (AFR)

AF:

0.0000426

AC:

AN:

23468

American (AMR)

AF:

0.00

AC:

AN:

8918

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

2798

East Asian (EAS)

AF:

0.00

AC:

AN:

2856

South Asian (SAS)

AF:

0.00

AC:

AN:

2446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2610

Middle Eastern (MID)

AF:

0.00485

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.000174

AC:

AN:

51758

Other (OTH)

AF:

0.000774

AC:

AN:

1292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.622

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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

3.9

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-TAAAAAAAA

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