rs104895482

Positions:

• chr16-50711298-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001370466.1(NOD2):​c.1306C>G​(p.Pro436Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOD2 NM_001370466.1 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.805

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17256466).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.1306C>G	p.Pro436Ala	missense_variant	4/12	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.1306C>G	p.Pro436Ala	missense_variant	4/12		NM_001370466.1	ENSP00000495993.1
NOD2	ENST00000300589.6	c.1387C>G	p.Pro463Ala	missense_variant	4/12	1		ENSP00000300589.2
NOD2	ENST00000641284.2	n.1306C>G		non_coding_transcript_exon_variant	4/6			ENSP00000493088.1
NOD2	ENST00000646677.2	n.1306C>G		non_coding_transcript_exon_variant	4/13			ENSP00000496533.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

Blau syndrome Other:1

not provided, no classification provided

literature only

Unité médicale des maladies autoinflammatoires, CHRU Montpellier

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	11
DANN	Uncertain	0.98
DEOGEN2	Benign	0.31	.;T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.75	T;T
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.7	.;L
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.6	.;D
REVEL	Benign	0.11
Sift	Benign	0.19	.;T
Sift4G	Benign	0.13	.;T
Polyphen		0.41	B;B
Vest4		0.14
MutPred		0.43		.;Gain of catalytic residue at P463 (P = 0.0276);
MVP		0.74
MPC		0.12
ClinPred		0.47	T
GERP RS		4.1
Varity_R		0.096
gMVP		0.22

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

Other links and lift over

dbSNP: rs104895482; hg19: chr16-50745209;