rs2829876

Positions:

• chr21-25713512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021219.4(JAM2):​c.865-1128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 138,194 control chromosomes in the GnomAD database, including 794 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 0.11 (794 hom., cov: 29)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

Genes affected

JAM2 (HGNC:14686): (junctional adhesion molecule 2) This gene belongs to the immunoglobulin superfamily, and the junctional adhesion molecule (JAM) family. The protein encoded by this gene is a type I membrane protein that is localized at the tight junctions of both epithelial and endothelial cells. It acts as an adhesive ligand for interacting with a variety of immune cell types, and may play a role in lymphocyte homing to secondary lymphoid organs. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2012]

JAM2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4	c.865-1128C>T		intron_variant		ENST00000480456.6	NP_067042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.865-1128C>T		intron_variant		1	NM_021219.4	ENSP00000420419.1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 14589 AN: 138068 Hom.: 784 Cov.: 29

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0148

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.106 AC: 14628 AN: 138194 Hom.: 794 Cov.: 29 AF XY: 0.109 AC XY: 7212 AN XY: 66228

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.0953

Gnomad4 ASJ AF: 0.0969

Gnomad4 EAS AF: 0.0405

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.0884

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0940 Hom.: 111

Bravo AF: 0.0976

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.51

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: rs2829876; hg19: chr21-27085824;