rs104895429

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001370466.1(NOD2):ā€‹c.1160A>Cā€‹(p.Asn387Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,614,004 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NOD2
NM_001370466.1 missense

Scores

11
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.70
Variant links:
Genes affected
NOD2 (HGNC:5331): (nucleotide binding oligomerization domain containing 2) This gene is a member of the Nod1/Apaf-1 family and encodes a protein with two caspase recruitment (CARD) domains and six leucine-rich repeats (LRRs). The protein is primarily expressed in the peripheral blood leukocytes. It plays a role in the immune response to intracellular bacterial lipopolysaccharides (LPS) by recognizing the muramyl dipeptide (MDP) derived from them and activating the NFKB protein. Mutations in this gene have been associated with Crohn disease and Blau syndrome. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOD2NM_001370466.1 linkuse as main transcriptc.1160A>C p.Asn387Thr missense_variant 4/12 ENST00000647318.2 NP_001357395.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOD2ENST00000647318.2 linkuse as main transcriptc.1160A>C p.Asn387Thr missense_variant 4/12 NM_001370466.1 ENSP00000495993 P1Q9HC29-2
NOD2ENST00000300589.6 linkuse as main transcriptc.1241A>C p.Asn414Thr missense_variant 4/121 ENSP00000300589 Q9HC29-1
NOD2ENST00000641284.2 linkuse as main transcriptc.1160A>C p.Asn387Thr missense_variant, NMD_transcript_variant 4/6 ENSP00000493088
NOD2ENST00000646677.2 linkuse as main transcriptc.1160A>C p.Asn387Thr missense_variant, NMD_transcript_variant 4/13 ENSP00000496533

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251288
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135856
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:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461832
Hom.:
0
Cov.:
39
AF XY:
0.00000138
AC XY:
1
AN XY:
727216
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152172
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74334
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:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.015
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Benign
0.97
DEOGEN2
Benign
0.33
.;T
Eigen
Uncertain
0.37
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.81
T;T
M_CAP
Uncertain
0.28
D
MetaRNN
Uncertain
0.47
T;T
MetaSVM
Uncertain
-0.058
T
MutationAssessor
Benign
1.2
.;L
MutationTaster
Benign
0.96
D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.7
.;D
REVEL
Uncertain
0.44
Sift
Benign
0.25
.;T
Sift4G
Benign
0.44
.;T
Polyphen
0.53
P;D
Vest4
0.39
MutPred
0.52
.;Loss of helix (P = 0.0167);
MVP
0.89
MPC
0.20
ClinPred
0.45
T
GERP RS
5.4
Varity_R
0.28
gMVP
0.32

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: rs104895429; hg19: chr16-50745063; API