8-89784141-TAAAAAAAAAAAAAAAA-TAAAA

Variant names:

• chr8-89784141-TAAAAAAAAAAAA-T
• rs71268283
• NM_003821.6:c.1029+14_1029+25delAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003821.6(RIPK2):​c.1029+14_1029+25delAAAAAAAAAAAA variant causes a intron change. The variant allele was found at a frequency of 0.0000287 in 558,308 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_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 0.000010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000033 (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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+14_1029+25delAAAAAAAAAAAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+14_618+25delAAAAAAAAAAAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+14_516+25delAAAAAAAAAAAA		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+14_1029+25delAAAAAAAAAAAA		intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4

Frequencies

GnomAD3 genomes AF: 0.0000103 AC: 1 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: 0.0000193

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000325 AC: 15 AN: 461246 Hom.: 0 AF XY: 0.0000333 AC XY: 8 AN XY: 240042

African (AFR) AF: 0.000105 AC: 1 AN: 9518

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

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

East Asian (EAS) AF: 0.000339 AC: 7 AN: 20672

South Asian (SAS) AF: 0.00 AC: 0 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: 0.0000211 AC: 7 AN: 331314

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

GnomAD4 genome AF: 0.0000103 AC: 1 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: 0.0000193 AC: 1 AN: 51766

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;