8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAA

Position:

• chr8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000220751.5(RIPK2):​c.1029+2_1029+3insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (29 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: RIPK2 ENST00000220751.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 975 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+23_1029+25dupAAA		intron_variant		ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+23_618+25dupAAA		intron_variant			NP_001362289.1
RIPK2	XM_011517357.3	c.516+23_516+25dupAAA		intron_variant			XP_011515659.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+2_1029+3insAAA		splice_region_variant, intron_variant		1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+2_*668+3insAAA		splice_region_variant, intron_variant		1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1146 AN: 97032 Hom.: 29 Cov.: 0

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00371

Gnomad ASJ AF: 0.00107

Gnomad EAS AF: 0.000350

Gnomad SAS AF: 0.000407

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000502

Gnomad OTH AF: 0.0101

GnomAD4 exome AF: 0.00212 AC: 975 AN: 460418 Hom.: 1 Cov.: 0 AF XY: 0.00225 AC XY: 539 AN XY: 239608

Gnomad4 AFR exome AF: 0.0144

Gnomad4 AMR exome AF: 0.00345

Gnomad4 ASJ exome AF: 0.00331

Gnomad4 EAS exome AF: 0.00464

Gnomad4 SAS exome AF: 0.00665

Gnomad4 FIN exome AF: 0.000913

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00274

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0118 AC: 1147 AN: 97040 Hom.: 29 Cov.: 0 AF XY: 0.0119 AC XY: 527 AN XY: 44190

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.00370

Gnomad4 ASJ AF: 0.00107

Gnomad4 EAS AF: 0.000350

Gnomad4 SAS AF: 0.000409

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000502

Gnomad4 OTH AF: 0.0101

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;