Variant 16-50711227-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001370466.1(NOD2):c.1235G>T(p.Arg412Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,620 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

NOD2
NM_001370466.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.82

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 links:

NOD2 (HGNC:):

NOD2 links:

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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
NOD2	NM_001370466.1 linkuse as main transcript	c.1235G>T	p.Arg412Leu	missense_variant	4/12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NOD2	ENST00000647318.2 linkuse as main transcript	c.1235G>T	p.Arg412Leu	missense_variant	4/12		NM_001370466.1	ENSP00000495993.1	Q9HC29-2
NOD2	ENST00000300589.6 linkuse as main transcript	c.1316G>T	p.Arg439Leu	missense_variant	4/12	1		ENSP00000300589.2	Q9HC29-1
NOD2	ENST00000641284.2 linkuse as main transcript	n.1235G>T		non_coding_transcript_exon_variant	4/6			ENSP00000493088.1	A0A286YF65
NOD2	ENST00000646677.2 linkuse as main transcript	n.1235G>T		non_coding_transcript_exon_variant	4/13			ENSP00000496533.1	A0A286YF65

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250402

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135474

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461620

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727134

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:

0.0000116

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.051

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.46

.;T

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.56

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.86

D;D

M_CAP

Uncertain

0.28

MetaRNN

Uncertain

0.48

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Uncertain

2.0

.;M

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.8

.;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.013

.;D

Sift4G

Benign

0.079

.;T

Polyphen

0.66

P;P

Vest4

0.48

MutPred

0.51

.;Loss of MoRF binding (P = 0.0021);

MVP

0.86

MPC

0.36

ClinPred

0.77

GERP RS

2.2

Varity_R

0.33

gMVP

0.53

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over