8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAA

Position:

• chr8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003821.6(RIPK2):​c.1029+20_1029+25delAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0219 in 549,574 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000031 (0 hom., cov: 0)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: RIPK2 NM_003821.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.0266 (12016/452516) while in subpopulation MID AF= 0.0321 (53/1650). AF 95% confidence interval is 0.0285. There are 0 homozygotes in gnomad4_exome. There are 6339 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 12016 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+20_1029+25delAAAAAA		intron_variant		ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+20_618+25delAAAAAA		intron_variant			NP_001362289.1
RIPK2	XM_011517357.3	c.516+20_516+25delAAAAAA		intron_variant			XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+20_1029+25delAAAAAA		intron_variant		1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+20_*668+25delAAAAAA		intron_variant		1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.0000309 AC: 3 AN: 97058 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: 0.0000580

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0267 AC: 764 AN: 28604 Hom.: 0 AF XY: 0.0287 AC XY: 436 AN XY: 15204

Gnomad AFR exome AF: 0.0112

Gnomad AMR exome AF: 0.0334

Gnomad ASJ exome AF: 0.0178

Gnomad EAS exome AF: 0.0112

Gnomad SAS exome AF: 0.0214

Gnomad FIN exome AF: 0.0157

Gnomad NFE exome AF: 0.0341

Gnomad OTH exome AF: 0.0304

GnomAD4 exome AF: 0.0266 AC: 12016 AN: 452516 Hom.: 0 AF XY: 0.0269 AC XY: 6339 AN XY: 235246

Gnomad4 AFR exome AF: 0.0151

Gnomad4 AMR exome AF: 0.0280

Gnomad4 ASJ exome AF: 0.0233

Gnomad4 EAS exome AF: 0.00518

Gnomad4 SAS exome AF: 0.0184

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0290

Gnomad4 OTH exome AF: 0.0270

GnomAD4 genome AF: 0.0000309 AC: 3 AN: 97058 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 44186

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000580

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs71268283; hg19: chr8-90796369;