8-89784141-TAAAAAAAAAA-T

Variant names:

• chr8-89784141-TAAAAAAAAAA-T
• rs71268283
• NM_003821.6:c.1029+16_1029+25delAAAAAAAAAA

Variant summary

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

The NM_003821.6(RIPK2):​c.1029+16_1029+25delAAAAAAAAAA variant causes a intron change. The variant allele was found at a frequency of 0.000119 in 461,124 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92
• 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: NM_003821.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	NM_003821.6	MANE Select	c.1029+16_1029+25delAAAAAAAAAA		intron	N/A	NP_003812.1
	RIPK2	NM_001375360.1		c.618+16_618+25delAAAAAAAAAA		intron	N/A	NP_001362289.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.1029+16_1029+25delAAAAAAAAAA		intron	N/A	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.*668+16_*668+25delAAAAAAAAAA		intron	N/A	ENSP00000429271.1
	PARAIL	ENST00000814457.1		n.650-58510_650-58501delTTTTTTTTTT		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.000119 AC: 55 AN: 461124 Hom.: 0 AF XY: 0.000154 AC XY: 37 AN XY: 239984

⚠️ 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: 0.000181 AC: 2 AN: 11040

Ashkenazi Jewish (ASJ) AF: 0.000292 AC: 3 AN: 10274

East Asian (EAS) AF: 0.00 AC: 0 AN: 20670

South Asian (SAS) AF: 0.000193 AC: 5 AN: 25868

European-Finnish (FIN) AF: 0.0000702 AC: 2 AN: 28478

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

European-Non Finnish (NFE) AF: 0.000115 AC: 38 AN: 331240

Other (OTH) AF: 0.000224 AC: 5 AN: 22348

⚠️ 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.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.9

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;