8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr8-89784141-T-TAAAAAAAAAAA
• rs71268283
• NM_003821.6:c.1029+15_1029+25dupAAAAAAAAAAA

Variant summary

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

The NM_003821.6(RIPK2):​c.1029+15_1029+25dupAAAAAAAAAAA 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• Publications: 0 publications found

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]

PARAIL (HGNC:55545): (palmitic acid regulated anti-inflammatory lncRNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+15_1029+25dupAAAAAAAAAAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+15_618+25dupAAAAAAAAAAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+15_516+25dupAAAAAAAAAAA		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	c.1029+15_1029+25dupAAAAAAAAAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 97062 Hom.: 0 Cov.: 0

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: 3 AN: 461264 Hom.: 0 Cov.: 0 AF XY: 0.0000125 AC XY: 3 AN XY: 240056

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

African (AFR) AF: 0.00 AC: 0 AN: 9520

American (AMR) AF: 0.00 AC: 0 AN: 11044

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10276

East Asian (EAS) AF: 0.00 AC: 0 AN: 20676

South Asian (SAS) AF: 0.0000386 AC: 1 AN: 25888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28494

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1686

European-Non Finnish (NFE) AF: 0.00000604 AC: 2 AN: 331326

Other (OTH) AF: 0.00 AC: 0 AN: 22354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 97062 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44190

African (AFR) AF: 0.00 AC: 0 AN: 23440

American (AMR) AF: 0.00 AC: 0 AN: 8908

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2796

East Asian (EAS) AF: 0.00 AC: 0 AN: 2860

South Asian (SAS) AF: 0.00 AC: 0 AN: 2458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 51766

Other (OTH) AF: 0.00 AC: 0 AN: 1282

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

Other links and lift over

dbSNP: rs71268283; hg19: chr8-90796369;