chr8-89784141-T-TA

Position:

• chr8-89784141-T-TA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_003821.6(RIPK2):​c.1029+25dup 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. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.32 (5283 hom., cov: 0)
  • Exomes 𝑓: 0.075 (11 hom.)
• Consequence: RIPK2 NM_003821.6 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 8-89784141-T-TA is Benign according to our data. Variant chr8-89784141-T-TA is described in ClinVar as [Benign]. Clinvar id is 2867178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIPK2	ENST00000220751.5	c.1029+25dup		splice_region_variant, intron_variant		1	NM_003821.6	ENSP00000220751	P1
RIPK2	ENST00000522965.1	c.*668+25dup		splice_region_variant, intron_variant, NMD_transcript_variant		1		ENSP00000429271

Frequencies

GnomAD3 genomes AF: 0.324 AC: 31322 AN: 96572 Hom.: 5282 Cov.: 0

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.452

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.273

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.0323 AC: 925 AN: 28604 Hom.: 19 AF XY: 0.0305 AC XY: 463 AN XY: 15204

Gnomad AFR exome AF: 0.0380

Gnomad AMR exome AF: 0.0782

Gnomad ASJ exome AF: 0.0489

Gnomad EAS exome AF: 0.0809

Gnomad SAS exome AF: 0.0460

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.0215

Gnomad OTH exome AF: 0.0441

GnomAD4 exome AF: 0.0750 AC: 33709 AN: 449438 Hom.: 11 Cov.: 0 AF XY: 0.0754 AC XY: 17632 AN XY: 233904

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.0882

Gnomad4 ASJ exome AF: 0.107

Gnomad4 EAS exome AF: 0.130

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0538

Gnomad4 NFE exome AF: 0.0704

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.324 AC: 31320 AN: 96586 Hom.: 5283 Cov.: 0 AF XY: 0.320 AC XY: 14085 AN XY: 43948

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.327

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

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;