8-89780141-T-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_003821.6(RIPK2):āc.920T>Cā(p.Ile307Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000709 in 1,410,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 7.1e-7 ( 0 hom. )
Consequence
RIPK2
NM_003821.6 missense
NM_003821.6 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 6.88
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31211543).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RIPK2 | NM_003821.6 | c.920T>C | p.Ile307Thr | missense_variant | 7/11 | ENST00000220751.5 | NP_003812.1 | |
RIPK2 | NM_001375360.1 | c.509T>C | p.Ile170Thr | missense_variant | 6/10 | NP_001362289.1 | ||
RIPK2 | XM_011517357.3 | c.407T>C | p.Ile136Thr | missense_variant | 5/9 | XP_011515659.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RIPK2 | ENST00000220751.5 | c.920T>C | p.Ile307Thr | missense_variant | 7/11 | 1 | NM_003821.6 | ENSP00000220751 | P1 | |
RIPK2 | ENST00000522965.1 | c.*559T>C | 3_prime_UTR_variant, NMD_transcript_variant | 6/10 | 1 | ENSP00000429271 | ||||
RIPK2 | ENST00000518673.1 | n.54T>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 7.09e-7 AC: 1AN: 1410844Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 701212
GnomAD4 exome
AF:
AC:
1
AN:
1410844
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Cov.:
24
AF XY:
AC XY:
0
AN XY:
701212
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
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 | Jun 07, 2024 | The c.920T>C (p.I307T) alteration is located in exon 7 (coding exon 7) of the RIPK2 gene. This alteration results from a T to C substitution at nucleotide position 920, causing the isoleucine (I) at amino acid position 307 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0248);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.