8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAAAAAAA

Variant names:

• chr8-89784141-T-TAAAAAAAA
• rs71268283
• NM_003821.6:c.1029+18_1029+25dupAAAAAAAA

Variant summary

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

The ENST00000220751.5(RIPK2):​c.1029+2_1029+3insAAAAAAAA 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 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000013 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIPK2 ENST00000220751.5 splice_region, 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.

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+18_1029+25dupAAAAAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+18_618+25dupAAAAAAAA		intron	N/A	NP_001362289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+2_1029+3insAAAAAAAA		splice_region intron	N/A	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*668+2_*668+3insAAAAAAAA		splice_region intron	N/A	ENSP00000429271.1
	RIPK2	ENST00000929530.1		c.1089+2_1089+3insAAAAAAAA		splice_region intron	N/A	ENSP00000599589.1

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: 0.0000130 AC: 6 AN: 461260 Hom.: 0 Cov.: 0 AF XY: 0.0000125 AC XY: 3 AN XY: 240054

⚠️ 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: 0.0000121 AC: 4 AN: 331322

Other (OTH) AF: 0.0000447 AC: 1 AN: 22354

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000559552), 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 v4.9

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;