8-89769900-A-T

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

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.99
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 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
RIPK2NM_003821.6 linkuse as main transcriptc.612A>T p.Ser204= synonymous_variant 4/11 ENST00000220751.5
RIPK2NM_001375360.1 linkuse as main transcriptc.201A>T p.Ser67= synonymous_variant 3/10
RIPK2XM_011517357.3 linkuse as main transcriptc.99A>T p.Ser33= synonymous_variant 2/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RIPK2ENST00000220751.5 linkuse as main transcriptc.612A>T p.Ser204= synonymous_variant 4/111 NM_003821.6 P1O43353-1
RIPK2ENST00000522965.1 linkuse as main transcriptc.*251A>T 3_prime_UTR_variant, NMD_transcript_variant 3/101

Frequencies

GnomAD3 genomes
AF:
0.0100
AC:
1520
AN:
151840
Hom.:
32
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0344
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00500
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00260
AC:
642
AN:
246756
Hom.:
8
AF XY:
0.00192
AC XY:
257
AN XY:
133636
show subpopulations
Gnomad AFR exome
AF:
0.0329
Gnomad AMR exome
AF:
0.00263
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000993
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000197
Gnomad OTH exome
AF:
0.00150
GnomAD4 exome
AF:
0.00110
AC:
1595
AN:
1455674
Hom.:
13
Cov.:
31
AF XY:
0.000958
AC XY:
694
AN XY:
724156
show subpopulations
Gnomad4 AFR exome
AF:
0.0337
Gnomad4 AMR exome
AF:
0.00278
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000585
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000210
Gnomad4 OTH exome
AF:
0.00193
GnomAD4 genome
AF:
0.0100
AC:
1521
AN:
151958
Hom.:
32
Cov.:
32
AF XY:
0.00911
AC XY:
677
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.0343
Gnomad4 AMR
AF:
0.00500
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00347
Hom.:
5
Bravo
AF:
0.0114
Asia WGS
AF:
0.000867
AC:
4
AN:
3476
EpiCase
AF:
0.000110
EpiControl
AF:
0.000361

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 submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpMay 31, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
5.9
DANN
Benign
0.67
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs56257721; hg19: chr8-90782128; API