Genetic Variant RIPK2:c.1029+17_1029+25dupAAAAAAAAA (chr8-89784141-T-TAAAAAAAAA) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000220751.5(RIPK2):c.1029+2_1029+3insAAAAAAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000010 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000011 ( 0 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: Uncertain_significance. The variant received 0 ACMG points.

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+17_1029+25dupAAAAAAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+17_618+25dupAAAAAAAAA		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+2_1029+3insAAAAAAAAA	splice_region intron	N/A	ENSP00000220751.4
RIPK2	ENST00000522965.1	TSL:1	n.668+2_668+3insAAAAAAAAA	splice_region intron	N/A	ENSP00000429271.1
RIPK2	ENST00000929530.1		c.1089+2_1089+3insAAAAAAAAA	splice_region intron	N/A	ENSP00000599589.1

Frequencies

GnomAD3 genomes

AF:

0.0000103

AC:

AN:

97060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000193

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000108

AC:

AN:

461264

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

240056

show subpopulations

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

African (AFR)

AF:

0.000105

AC:

AN:

9520

American (AMR)

AF:

0.00

AC:

AN:

11044

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10276

East Asian (EAS)

AF:

0.00

AC:

AN:

20676

South Asian (SAS)

AF:

0.00

AC:

AN:

25888

European-Finnish (FIN)

AF:

0.00

AC:

AN:

28494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1686

European-Non Finnish (NFE)

AF:

0.0000121

AC:

AN:

331326

Other (OTH)

AF:

0.00

AC:

AN:

22354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0102811), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.355

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:

0.0000103

AC:

AN:

97060

Hom.:

Cov.:

AF XY:

0.0000226

AC XY:

AN XY:

44188

show subpopulations

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

African (AFR)

AF:

0.00

AC:

AN:

23440

American (AMR)

AF:

0.00

AC:

AN:

8908

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2796

East Asian (EAS)

AF:

0.00

AC:

AN:

2858

South Asian (SAS)

AF:

0.00

AC:

AN:

2458

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

222

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

51766

Other (OTH)

AF:

0.00

AC:

AN:

1282

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.225

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

Splicing

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

Publications

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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