rs200818100

Variant names:

• chr8-89762965-A-C
• rs200818100
• NM_003821.6:c.310A>C

Your query was ambiguous. Multiple possible variants found:

• chr8-89762965-A-C
• chr8-89762965-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_003821.6(RIPK2):​c.310A>C​(p.Asn104His) variant causes a missense change. The variant allele was found at a frequency of 0.0000288 in 1,353,120 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. N104D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000029 (0 hom.)
• Consequence: RIPK2 NM_003821.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.15
• Publications: 8 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 -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 39 AD gene.

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.310A>C	p.Asn104His	missense	Exon 2 of 11	NP_003812.1
	RIPK2	NM_001375360.1		c.-84-2376A>C		intron	N/A	NP_001362289.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RIPK2	ENST00000220751.5	TSL:1 MANE Select	c.310A>C	p.Asn104His	missense	Exon 2 of 11	ENSP00000220751.4
	RIPK2	ENST00000522965.1	TSL:1	n.174-2376A>C		intron	N/A	ENSP00000429271.1
	RIPK2	ENST00000929530.1		c.370A>C	p.Asn124His	missense	Exon 3 of 12	ENSP00000599589.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000288 AC: 39 AN: 1353120 Hom.: 0 Cov.: 28 AF XY: 0.0000301 AC XY: 20 AN XY: 665466

African (AFR) AF: 0.00 AC: 0 AN: 30758

American (AMR) AF: 0.00 AC: 0 AN: 35612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23534

East Asian (EAS) AF: 0.00 AC: 0 AN: 37130

South Asian (SAS) AF: 0.00 AC: 0 AN: 65694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5390

European-Non Finnish (NFE) AF: 0.0000362 AC: 38 AN: 1049684

Other (OTH) AF: 0.0000181 AC: 1 AN: 55310

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.034	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.55
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.028	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.60	T
MutationAssessor	Benign	0.39	N
PhyloP100		7.2
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Benign	0.032	D
Sift4G	Benign	0.38	T
Polyphen		1.0	D
Vest4		0.50
MutPred		0.47		Gain of disorder (P = 0.06)
MVP		0.84
MPC		2.2
ClinPred		0.92	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.55
Mutation Taster		=49/51	disease causing

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: rs200818100; hg19: chr8-90775193;