8-89762924-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_003821.6(RIPK2):ā€‹c.269T>Gā€‹(p.Phe90Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000163 in 1,533,666 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000033 ( 0 hom., cov: 32)
Exomes š‘“: 0.000014 ( 0 hom. )

Consequence

RIPK2
NM_003821.6 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.17
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RIPK2NM_003821.6 linkuse as main transcriptc.269T>G p.Phe90Cys missense_variant 2/11 ENST00000220751.5
RIPK2NM_001375360.1 linkuse as main transcriptc.-84-2417T>G intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIPK2ENST00000220751.5 linkuse as main transcriptc.269T>G p.Phe90Cys missense_variant 2/111 NM_003821.6 P1O43353-1
RIPK2ENST00000522965.1 linkuse as main transcriptc.174-2417T>G intron_variant, NMD_transcript_variant 1

Frequencies

GnomAD3 genomes
AF:
0.0000329
AC:
5
AN:
152130
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000130
AC:
3
AN:
229918
Hom.:
0
AF XY:
0.00000801
AC XY:
1
AN XY:
124874
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000279
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000145
AC:
20
AN:
1381536
Hom.:
0
Cov.:
28
AF XY:
0.0000102
AC XY:
7
AN XY:
683394
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000169
Gnomad4 OTH exome
AF:
0.0000177
GnomAD4 genome
AF:
0.0000329
AC:
5
AN:
152130
Hom.:
0
Cov.:
32
AF XY:
0.0000404
AC XY:
3
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000736
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000254
Hom.:
0

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 29, 2023The c.269T>G (p.F90C) alteration is located in exon 2 (coding exon 2) of the RIPK2 gene. This alteration results from a T to G substitution at nucleotide position 269, causing the phenylalanine (F) at amino acid position 90 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.19
CADD
Pathogenic
27
DANN
Uncertain
0.99
DEOGEN2
Benign
0.39
T
Eigen
Uncertain
0.41
Eigen_PC
Uncertain
0.48
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.79
T
M_CAP
Benign
0.031
D
MetaRNN
Uncertain
0.67
D
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.0
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.79
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.28
Sift
Uncertain
0.026
D
Sift4G
Benign
0.14
T
Polyphen
0.89
P
Vest4
0.69
MutPred
0.49
Loss of stability (P = 0.0508);
MVP
0.67
MPC
2.2
ClinPred
0.91
D
GERP RS
5.3
Varity_R
0.68
gMVP
0.84

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1374082877; hg19: chr8-90775152; API