8-89769900-A-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003821.6(RIPK2):c.612A>T(p.Ser204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00194 in 1,607,632 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.010 ( 32 hom., cov: 32)
Exomes 𝑓: 0.0011 ( 13 hom. )
Consequence
RIPK2
NM_003821.6 synonymous
NM_003821.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.99
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 Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 8-89769900-A-T is Benign according to our data. Variant chr8-89769900-A-T is described in ClinVar as [Benign]. Clinvar id is 707947.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.99 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1521/151958) while in subpopulation AFR AF= 0.0343 (1424/41510). AF 95% confidence interval is 0.0328. There are 32 homozygotes in gnomad4. There are 677 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 1521 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RIPK2 | NM_003821.6 | c.612A>T | p.Ser204= | synonymous_variant | 4/11 | ENST00000220751.5 | |
RIPK2 | NM_001375360.1 | c.201A>T | p.Ser67= | synonymous_variant | 3/10 | ||
RIPK2 | XM_011517357.3 | c.99A>T | p.Ser33= | synonymous_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RIPK2 | ENST00000220751.5 | c.612A>T | p.Ser204= | synonymous_variant | 4/11 | 1 | NM_003821.6 | P1 | |
RIPK2 | ENST00000522965.1 | c.*251A>T | 3_prime_UTR_variant, NMD_transcript_variant | 3/10 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0100 AC: 1520AN: 151840Hom.: 32 Cov.: 32
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GnomAD3 exomes AF: 0.00260 AC: 642AN: 246756Hom.: 8 AF XY: 0.00192 AC XY: 257AN XY: 133636
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GnomAD4 exome AF: 0.00110 AC: 1595AN: 1455674Hom.: 13 Cov.: 31 AF XY: 0.000958 AC XY: 694AN XY: 724156
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GnomAD4 genome AF: 0.0100 AC: 1521AN: 151958Hom.: 32 Cov.: 32 AF XY: 0.00911 AC XY: 677AN XY: 74306
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 31, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at