rs2076756

Positions:

• chr16-50722970-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001370466.1(NOD2):​c.2717+265A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 151,902 control chromosomes in the GnomAD database, including 2,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.17 (2890 hom., cov: 31)
• Consequence: NOD2 NM_001370466.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.293

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-50722970-A-G is Benign according to our data. Variant chr16-50722970-A-G is described in ClinVar as [Benign]. Clinvar id is 1261773.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.251 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOD2	NM_001370466.1	c.2717+265A>G		intron_variant		ENST00000647318.2	NP_001357395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOD2	ENST00000647318.2	c.2717+265A>G		intron_variant			NM_001370466.1	ENSP00000495993	P1

Frequencies

GnomAD3 genomes AF: 0.171 AC: 26009 AN: 151784 Hom.: 2889 Cov.: 31

Gnomad AFR AF: 0.0600

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.00813

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.254

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.171 AC: 26017 AN: 151902 Hom.: 2890 Cov.: 31 AF XY: 0.166 AC XY: 12342 AN XY: 74258

Gnomad4 AFR AF: 0.0601

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.00815

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.254

Gnomad4 OTH AF: 0.204

Alfa AF: 0.238 Hom.: 9984

Bravo AF: 0.165

Asia WGS AF: 0.0730 AC: 260 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.75

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: rs2076756; hg19: chr16-50756881;