rs754761524

chr16-50711419-AGG-Achr16-50711419-AGG-AGchr16-50711419-AGG-AGGG

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1

The NM_001370466.1(NOD2):c.1433_1434del(p.Gly478ValfsTer73) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. E476E) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NOD2 NM_001370466.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.211

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]

ACMG classification

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOD2	NM_001370466.1	c.1433_1434del	p.Gly478ValfsTer73	frameshift_variant	4/12	ENST00000647318.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOD2	ENST00000647318.2	c.1433_1434del	p.Gly478ValfsTer73	frameshift_variant	4/12		NM_001370466.1	P1
NOD2	ENST00000300589.6	c.1514_1515del	p.Gly505ValfsTer73	frameshift_variant	4/12	1
NOD2	ENST00000641284.2	c.1433_1434del	p.Gly478ValfsTer73	frameshift_variant, NMD_transcript_variant	4/6
NOD2	ENST00000646677.2	c.1433_1434del	p.Gly478ValfsTer73	frameshift_variant, NMD_transcript_variant	4/13

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-50745330;