8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Position:

• chr8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_003821.6(RIPK2):​c.1029+21_1029+25delAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 545,656 control chromosomes in the GnomAD database, including 16 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.072 (16 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.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0778 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+21_1029+25delAAAAA		intron_variant		ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+21_618+25delAAAAA		intron_variant			NP_001362289.1
RIPK2	XM_011517357.3	c.516+21_516+25delAAAAA		intron_variant			XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+21_1029+25delAAAAA		intron_variant		1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+21_*668+25delAAAAA		intron_variant		1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.000155 AC: 15 AN: 97044 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000337

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00153

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000155

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0650 AC: 1859 AN: 28604 Hom.: 2 AF XY: 0.0647 AC XY: 984 AN XY: 15204

Gnomad AFR exome AF: 0.0348

Gnomad AMR exome AF: 0.0818

Gnomad ASJ exome AF: 0.0507

Gnomad EAS exome AF: 0.0248

Gnomad SAS exome AF: 0.0417

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0782

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0721 AC: 32331 AN: 448604 Hom.: 16 AF XY: 0.0718 AC XY: 16736 AN XY: 233228

Gnomad4 AFR exome AF: 0.0460

Gnomad4 AMR exome AF: 0.0681

Gnomad4 ASJ exome AF: 0.0531

Gnomad4 EAS exome AF: 0.0187

Gnomad4 SAS exome AF: 0.0490

Gnomad4 FIN exome AF: 0.0745

Gnomad4 NFE exome AF: 0.0786

Gnomad4 OTH exome AF: 0.0707

GnomAD4 genome AF: 0.000155 AC: 15 AN: 97052 Hom.: 0 Cov.: 0 AF XY: 0.000181 AC XY: 8 AN XY: 44198

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000337

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00153

Gnomad4 NFE AF: 0.000155

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;