chr8-89772777-CTA-ATC

Variant names:

• chr8-89772777-CTA-ATC
• NM_003821.6:c.802_804delCTAinsATC
• RIPK2 p.Leu268Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003821.6(RIPK2):​c.802_804delCTAinsATC​(p.Leu268Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L268V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RIPK2 NM_003821.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.54
• Publications: 0 publications found

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]

PARAIL (HGNC:55545): (palmitic acid regulated anti-inflammatory lncRNA)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003821.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	NM_003821.6	MANE Select	c.802_804delCTAinsATC	p.Leu268Ile	missense	N/A	NP_003812.1	O43353-1
	RIPK2	NM_001375360.1		c.391_393delCTAinsATC	p.Leu131Ile	missense	N/A	NP_001362289.1	O43353-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.802_804delCTAinsATC	p.Leu268Ile	missense	N/A	ENSP00000220751.4	O43353-1
	RIPK2	ENST00000522965.1	TSL:1	n.*441_*443delCTAinsATC		non_coding_transcript_exon	Exon 5 of 10	ENSP00000429271.1	E7ERW9
	RIPK2	ENST00000522965.1	TSL:1	n.*441_*443delCTAinsATC		3_prime_UTR	Exon 5 of 10	ENSP00000429271.1	E7ERW9

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.5

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr8-90785005;