8-89762924-T-G
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003821.6(RIPK2):āc.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
NM_003821.6 missense
Scores
3
6
10
Clinical Significance
Conservation
PhyloP100: 6.17
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]
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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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RIPK2 | NM_003821.6 | c.269T>G | p.Phe90Cys | missense_variant | 2/11 | ENST00000220751.5 | NP_003812.1 | |
RIPK2 | NM_001375360.1 | c.-84-2417T>G | intron_variant | NP_001362289.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RIPK2 | ENST00000220751.5 | c.269T>G | p.Phe90Cys | missense_variant | 2/11 | 1 | NM_003821.6 | ENSP00000220751 | P1 | |
RIPK2 | ENST00000522965.1 | c.174-2417T>G | intron_variant, NMD_transcript_variant | 1 | ENSP00000429271 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000130 AC: 3AN: 229918Hom.: 0 AF XY: 0.00000801 AC XY: 1AN XY: 124874
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GnomAD4 exome AF: 0.0000145 AC: 20AN: 1381536Hom.: 0 Cov.: 28 AF XY: 0.0000102 AC XY: 7AN XY: 683394
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74310
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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 submitter | clinical testing | Ambry Genetics | Sep 29, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
T
PROVEAN
Uncertain
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of stability (P = 0.0508);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at