rs976567823

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022162.3(NOD2):c.7G>C(p.Glu3Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,556,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000078 ( 0 hom. )

Consequence

NOD2
NM_022162.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.812

Publications

0 publications found

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]

NOD2 Gene-Disease associations (from GenCC):

Blau syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Illumina
inflammatory bowel disease 1
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

NOD2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055886).

BS2

High AC in GnomAd4 at 7 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022162.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD2	NM_001370466.1	MANE Select	c.-8-2238G>C		intron	N/A	NP_001357395.1	Q9HC29-2
NOD2	NM_022162.3		c.7G>C	p.Glu3Gln	missense	Exon 1 of 12	NP_071445.1	Q9HC29-1
NOD2	NR_163434.1		n.58-2238G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOD2	ENST00000300589.6	TSL:1	c.7G>C	p.Glu3Gln	missense	Exon 1 of 12	ENSP00000300589.2	Q9HC29-1
NOD2	ENST00000527070.5	TSL:1	c.-798G>C		5_prime_UTR	Exon 1 of 4	ENSP00000435149.2	E9PLF7
NOD2	ENST00000647318.2	MANE Select	c.-8-2238G>C		intron	N/A	ENSP00000495993.1	Q9HC29-2

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000603

AC:

AN:

165952

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000105

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000783

AC:

AN:

1404652

Hom.:

Cov.:

AF XY:

0.00000433

AC XY:

AN XY:

693420

show subpopulations

African (AFR)

AF:

0.000251

AC:

AN:

31904

American (AMR)

AF:

0.00

AC:

AN:

36494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25220

East Asian (EAS)

AF:

0.00

AC:

AN:

36256

South Asian (SAS)

AF:

0.00

AC:

AN:

79502

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49648

Middle Eastern (MID)

AF:

0.000352

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1081700

Other (OTH)

AF:

0.0000172

AC:

AN:

58242

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.000169

AC:

AN:

41442

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000416

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Regional enteritis;C5201146:Blau syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.088

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.5

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.071

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.098

LIST_S2

Benign

0.37

M_CAP

Benign

0.010

MetaRNN

Benign

0.056

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PhyloP100

0.81

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.10

REVEL

Benign

0.15

Sift

Pathogenic

0.0

Polyphen

0.032

Vest4

0.096

MutPred

0.098

Loss of solvent accessibility (P = 0.1868)

MVP

0.65

MPC

0.22

ClinPred

0.16

GERP RS

-2.7

PromoterAI

-0.063

Neutral

(source)

Varity_R

0.21

gMVP

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over