Genetic Variant RIPK2:c.1029+14_1029+25dupAAAAAAAAAAAA (chr8-89784141-T-TAAAAAAAAAAAA) – 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+14_1029+25dupAAAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000065 ( 0 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:

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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+14_1029+25dupAAAAAAAAAAAA	intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1 link	c.618+14_618+25dupAAAAAAAAAAAA	intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3 link	c.516+14_516+25dupAAAAAAAAAAAA	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+14_1029+25dupAAAAAAAAAAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

97054

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000650

AC:

AN:

461262

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:

0.00

AC:

AN:

9520

American (AMR)

AF:

0.00

AC:

AN:

11042

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10276

East Asian (EAS)

AF:

0.00

AC:

AN:

20676

South Asian (SAS)

AF:

0.0000386

AC:

AN:

25888

European-Finnish (FIN)

AF:

0.0000351

AC:

AN:

28494

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1686

European-Non Finnish (NFE)

AF:

0.00000302

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 = 0.00000547158), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.342

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

97062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

44202

African (AFR)

AF:

0.00

AC:

AN:

23468

American (AMR)

AF:

0.00

AC:

AN:

8916

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2796

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:

0.00

AC:

AN:

206

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

51752

Other (OTH)

AF:

0.00

AC:

AN:

1292

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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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8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over