Genetic Variant RIPK2:c.1029+15_1029+25delAAAAAAAAAAA (chr8-89784141-TAAAAAAAAAAA-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+13delAAAAAAAAAAA variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000435 in 558,286 control chromosomes in the GnomAD database, including 2 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00026 ( 2 hom., cov: 0)

Exomes 𝑓: 0.00047 ( 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 25 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+15_1029+25delAAAAAAAAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+15_618+25delAAAAAAAAAAA		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+13delAAAAAAAAAAA	splice_region intron	N/A	ENSP00000220751.4
RIPK2	ENST00000522965.1	TSL:1	n.668+3_668+13delAAAAAAAAAAA	splice_region intron	N/A	ENSP00000429271.1
RIPK2	ENST00000929530.1		c.1089+3_1089+13delAAAAAAAAAAA	splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes

AF:

0.000258

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:

0.00

Gnomad EAS

AF:

0.00664

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000383

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000773

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000473

AC:

218

AN:

461214

Hom.:

AF XY:

0.000458

AC XY:

110

AN XY:

240026

show subpopulations

African (AFR)

AF:

0.000105

AC:

AN:

9520

American (AMR)

AF:

0.00

AC:

AN:

11042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10276

East Asian (EAS)

AF:

0.00929

AC:

192

AN:

20672

South Asian (SAS)

AF:

0.000270

AC:

AN:

25886

European-Finnish (FIN)

AF:

0.0000702

AC:

AN:

28486

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1686

European-Non Finnish (NFE)

AF:

0.0000392

AC:

AN:

331292

Other (OTH)

AF:

0.000134

AC:

AN:

22354

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000258

AC:

AN:

97072

Hom.:

Cov.:

AF XY:

0.000339

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:

0.00

AC:

AN:

2796

East Asian (EAS)

AF:

0.00665

AC:

AN:

2856

South Asian (SAS)

AF:

0.00

AC:

AN:

2446

European-Finnish (FIN)

AF:

0.000383

AC:

AN:

2612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.0000773

AC:

AN:

51758

Other (OTH)

AF:

0.00

AC:

AN:

1292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.661

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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8-89784141-TAAAAAAAAAAAAAAAA-TAAAAA

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