8-89769900-A-G

Variant names:

• chr8-89769900-A-G
• rs56257721
• NM_003821.6:c.612A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003821.6(RIPK2):​c.612A>G​(p.Ser204Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S204S) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RIPK2 NM_003821.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.

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.612A>G	p.Ser204Ser	synonymous	Exon 4 of 11	NP_003812.1	O43353-1
	RIPK2	NM_001375360.1		c.201A>G	p.Ser67Ser	synonymous	Exon 3 of 10	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.612A>G	p.Ser204Ser	synonymous	Exon 4 of 11	ENSP00000220751.4	O43353-1
	RIPK2	ENST00000522965.1	TSL:1	n.*251A>G		non_coding_transcript_exon	Exon 3 of 10	ENSP00000429271.1	E7ERW9
	RIPK2	ENST00000522965.1	TSL:1	n.*251A>G		3_prime_UTR	Exon 3 of 10	ENSP00000429271.1	E7ERW9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455684 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 724160

African (AFR) AF: 0.00 AC: 0 AN: 32992

American (AMR) AF: 0.00 AC: 0 AN: 43896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39272

South Asian (SAS) AF: 0.00 AC: 0 AN: 85500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1108850

Other (OTH) AF: 0.0000166 AC: 1 AN: 60130

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.4
DANN	Benign	0.72
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs56257721; hg19: chr8-90782128;