Genetic Variant RIPK2:c.1029+23_1029+25dupAAA (chr8-89784141-T-TAAA) – 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+23_1029+25dupAAA variant causes a 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 0.012 ( 29 hom., cov: 0)

Exomes 𝑓: 0.0021 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RIPK2
NM_003821.6 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:

Genome browser will be placed here

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+23_1029+25dupAAA	intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1 link	c.618+23_618+25dupAAA	intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3 link	c.516+23_516+25dupAAA	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+23_1029+25dupAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes

AF:

0.0118

AC:

1146

AN:

97032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00371

Gnomad ASJ

AF:

0.00107

Gnomad EAS

AF:

0.000350

Gnomad SAS

AF:

0.000407

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000502

Gnomad OTH

AF:

0.0101

GnomAD4 exome

AF:

0.00212

AC:

975

AN:

460418

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

539

AN XY:

239608

show subpopulations

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

African (AFR)

AF:

0.0144

AC:

135

AN:

9376

American (AMR)

AF:

0.00345

AC:

AN:

11006

Ashkenazi Jewish (ASJ)

AF:

0.00331

AC:

AN:

10258

East Asian (EAS)

AF:

0.00464

AC:

AN:

20488

South Asian (SAS)

AF:

0.00665

AC:

172

AN:

25848

European-Finnish (FIN)

AF:

0.000913

AC:

AN:

28476

Middle Eastern (MID)

AF:

0.00237

AC:

AN:

1686

European-Non Finnish (NFE)

AF:

0.00124

AC:

410

AN:

331014

Other (OTH)

AF:

0.00274

AC:

AN:

22266

⚠️ 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: 0.343

Heterozygous variant carriers

122

184

245

306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0118

AC:

1147

AN:

97040

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

527

AN XY:

44190

show subpopulations

African (AFR)

AF:

0.0456

AC:

1070

AN:

23450

American (AMR)

AF:

0.00370

AC:

AN:

8916

Ashkenazi Jewish (ASJ)

AF:

0.00107

AC:

AN:

2794

East Asian (EAS)

AF:

0.000350

AC:

AN:

2856

South Asian (SAS)

AF:

0.000409

AC:

AN:

2446

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.000502

AC:

AN:

51750

Other (OTH)

AF:

0.0101

AC:

AN:

1292

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.531

Heterozygous variant carriers

143

190

238

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.60

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-TAAAAAAAAAAAAAAAAAAA

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