8-89784141-TAAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAA

Variant names:

• chr8-89784141-TA-T
• rs71268283
• NM_003821.6:c.1029+25delA

Variant summary

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

The ENST00000220751.5(RIPK2):​c.1029+3delA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 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 0.098 (424 hom., cov: 0)
  • Exomes 𝑓: 0.066 (9 hom.)
• 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 Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0984 AC: 9524 AN: 96758 Hom.: 426 Cov.: 0

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00694

Gnomad AMR AF: 0.0652

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.0803

Gnomad MID AF: 0.0856

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0828

GnomAD4 exome AF: 0.0656 AC: 29599 AN: 451060 Hom.: 9 Cov.: 0 AF XY: 0.0661 AC XY: 15516 AN XY: 234726

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.0702

Gnomad4 ASJ exome AF: 0.0753

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.0786

Gnomad4 FIN exome AF: 0.0487

Gnomad4 NFE exome AF: 0.0567

Gnomad4 OTH exome AF: 0.0755

GnomAD4 genome AF: 0.0984 AC: 9518 AN: 96766 Hom.: 424 Cov.: 0 AF XY: 0.102 AC XY: 4511 AN XY: 44062

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.0651

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.277

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.0803

Gnomad4 NFE AF: 0.0576

Gnomad4 OTH AF: 0.0822

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;