8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAA

Variant names:

• chr8-89784141-TAAAA-T
• rs71268283
• NM_003821.6:c.1029+22_1029+25delAAAA

Variant summary

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

The ENST00000220751.5(RIPK2):​c.1029+3_1029+6delAAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 547,146 control chromosomes in the GnomAD database, including 100 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (100 hom.)
• Consequence: RIPK2 ENST00000220751.5 splice_region, 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 = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RIPK2	NM_003821.6	c.1029+22_1029+25delAAAA		intron_variant	Intron 8 of 10	ENST00000220751.5	NP_003812.1
RIPK2	NM_001375360.1	c.618+22_618+25delAAAA		intron_variant	Intron 7 of 9		NP_001362289.1
RIPK2	XM_011517357.3	c.516+22_516+25delAAAA		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+3_1029+6delAAAA		splice_region_variant, intron_variant	Intron 8 of 10	1	NM_003821.6	ENSP00000220751.4
RIPK2	ENST00000522965.1	n.*668+3_*668+6delAAAA		splice_region_variant, intron_variant	Intron 7 of 9	1		ENSP00000429271.1

Frequencies

GnomAD3 genomes AF: 0.000763 AC: 74 AN: 97030 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000853

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00112

Gnomad ASJ AF: 0.000358

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000814

Gnomad FIN AF: 0.00345

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000599

Gnomad OTH AF: 0.000780

GnomAD3 exomes AF: 0.0789 AC: 2258 AN: 28604 Hom.: 11 AF XY: 0.0764 AC XY: 1162 AN XY: 15204

Gnomad AFR exome AF: 0.0663

Gnomad AMR exome AF: 0.106

Gnomad ASJ exome AF: 0.0649

Gnomad EAS exome AF: 0.0531

Gnomad SAS exome AF: 0.0520

Gnomad FIN exome AF: 0.0688

Gnomad NFE exome AF: 0.0880

Gnomad OTH exome AF: 0.0866

GnomAD4 exome AF: 0.125 AC: 56156 AN: 450108 Hom.: 100 AF XY: 0.123 AC XY: 28721 AN XY: 234040

Gnomad4 AFR exome AF: 0.0857

Gnomad4 AMR exome AF: 0.104

Gnomad4 ASJ exome AF: 0.0968

Gnomad4 EAS exome AF: 0.0473

Gnomad4 SAS exome AF: 0.0845

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.000763 AC: 74 AN: 97038 Hom.: 0 Cov.: 0 AF XY: 0.00102 AC XY: 45 AN XY: 44182

Gnomad4 AFR AF: 0.000852

Gnomad4 AMR AF: 0.00112

Gnomad4 ASJ AF: 0.000358

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000818

Gnomad4 FIN AF: 0.00345

Gnomad4 NFE AF: 0.000599

Gnomad4 OTH AF: 0.000774

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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;