16-50725636-A-G

Variant names:

• chr16-50725636-A-G
• rs1077861
• NM_001370466.1:c.2885+64A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001370466.1(NOD2):​c.2885+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000061 in 1,147,282 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44
• Publications: 0 publications found

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: ClinGen, Orphanet, Genomics England PanelApp, G2P, Illumina, Labcorp Genetics (formerly Invitae)
• inflammatory bowel disease 1

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 7 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2885+64A>G		intron_variant	Intron 10 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2885+64A>G		intron_variant	Intron 10 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000610 AC: 7 AN: 1147282 Hom.: 0 AF XY: 0.00000512 AC XY: 3 AN XY: 585748

African (AFR) AF: 0.00 AC: 0 AN: 27122

American (AMR) AF: 0.00 AC: 0 AN: 44016

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24018

East Asian (EAS) AF: 0.00 AC: 0 AN: 37942

South Asian (SAS) AF: 0.00 AC: 0 AN: 79546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52514

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4890

European-Non Finnish (NFE) AF: 0.00000846 AC: 7 AN: 827320

Other (OTH) AF: 0.00 AC: 0 AN: 49914

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.4
DANN	Benign	0.22
PhyloP100		-2.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.38		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.38		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1077861; hg19: chr16-50759547;