16-50724927-T-C

Variant names:

• chr16-50724927-T-C
• rs1861756
• NM_001370466.1:c.2802-562T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370466.1(NOD2):​c.2802-562T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.944 in 152,298 control chromosomes in the GnomAD database, including 67,949 homozygotes. 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: 𝑓 0.94 (67949 hom., cov: 32)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.466
• Publications: 1 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2802-562T>C		intron_variant	Intron 9 of 11	ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2802-562T>C		intron_variant	Intron 9 of 11		NM_001370466.1	ENSP00000495993.1

Frequencies

GnomAD3 genomes AF: 0.944 AC: 143600 AN: 152180 Hom.: 67888 Cov.: 32

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.932

Gnomad AMR AF: 0.964

Gnomad ASJ AF: 0.974

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.972

Gnomad FIN AF: 0.890

Gnomad MID AF: 0.981

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.955

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

GnomAD4 genome AF: 0.944 AC: 143721 AN: 152298 Hom.: 67949 Cov.: 32 AF XY: 0.944 AC XY: 70300 AN XY: 74458

African (AFR) AF: 0.985 AC: 40924 AN: 41564

American (AMR) AF: 0.964 AC: 14747 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.974 AC: 3383 AN: 3472

East Asian (EAS) AF: 0.999 AC: 5178 AN: 5182

South Asian (SAS) AF: 0.972 AC: 4690 AN: 4824

European-Finnish (FIN) AF: 0.890 AC: 9441 AN: 10608

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62201 AN: 68026

Other (OTH) AF: 0.955 AC: 2021 AN: 2116

Alfa AF: 0.946 Hom.: 42819

Bravo AF: 0.951

Asia WGS AF: 0.986 AC: 3429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.1
DANN	Benign	0.85
PhyloP100		-0.47
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1861756; hg19: chr16-50758838;