Genetic Variant RIPK2:c.1029+21_1029+25delAAAAA (chr8-89784141-TAAAAA-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_003821.6(RIPK2):c.1029+21_1029+25delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 545,656 control chromosomes in the GnomAD database, including 16 homozygotes. There is a variant allele frequency bias in the population database for this variant (GnomAd4), 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 0.00015 ( 0 hom., cov: 0)

Exomes 𝑓: 0.072 ( 16 hom. )

Consequence

RIPK2
NM_003821.6 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
RIPK2	NM_003821.6 link	c.1029+21_1029+25delAAAAA	intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1 link	c.618+21_618+25delAAAAA	intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3 link	c.516+21_516+25delAAAAA	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+21_1029+25delAAAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

97044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000337

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00153

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000155

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0650

AC:

1859

AN:

28604

AF XY:

0.0647

show subpopulations

Gnomad AFR exome

AF:

0.0348

Gnomad AMR exome

AF:

0.0818

Gnomad ASJ exome

AF:

0.0507

Gnomad EAS exome

AF:

0.0248

Gnomad FIN exome

AF:

0.0597

Gnomad NFE exome

AF:

0.0782

Gnomad OTH exome

AF:

0.0638

GnomAD4 exome

AF:

0.0721

AC:

32331

AN:

448604

Hom.:

AF XY:

0.0718

AC XY:

16736

AN XY:

233228

show subpopulations

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

African (AFR)

AF:

0.0460

AC:

427

AN:

9286

American (AMR)

AF:

0.0681

AC:

727

AN:

10672

Ashkenazi Jewish (ASJ)

AF:

0.0531

AC:

530

AN:

9984

East Asian (EAS)

AF:

0.0187

AC:

380

AN:

20268

South Asian (SAS)

AF:

0.0490

AC:

1237

AN:

25270

European-Finnish (FIN)

AF:

0.0745

AC:

2039

AN:

27366

Middle Eastern (MID)

AF:

0.0690

AC:

112

AN:

1624

European-Non Finnish (NFE)

AF:

0.0786

AC:

25346

AN:

322442

Other (OTH)

AF:

0.0707

AC:

1533

AN:

21692

⚠️ 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: 0.328

Heterozygous variant carriers

2165

4330

6494

8659

10824

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

97052

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

44198

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:

23468

American (AMR)

AF:

0.000337

AC:

AN:

8914

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2794

East Asian (EAS)

AF:

0.00

AC:

AN:

2856

South Asian (SAS)

AF:

0.00

AC:

AN:

2446

European-Finnish (FIN)

AF:

0.00153

AC:

AN:

2610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.000155

AC:

AN:

51746

Other (OTH)

AF:

0.00

AC:

AN:

1292

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00840681), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.395

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.2

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-TAAAAAAAAAAA

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