rs2051180

Positions:

• chr21-25696585-G-A

Variant summary

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

The NM_021219.4(JAM2):​c.395-2092G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,148 control chromosomes in the GnomAD database, including 1,740 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 0.13 (1740 hom., cov: 32)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930

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]

LOC124905002 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4	c.395-2092G>A		intron_variant		ENST00000480456.6	NP_067042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.395-2092G>A		intron_variant		1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.395-2092G>A		intron_variant		1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.287-2092G>A		intron_variant		2		ENSP00000318416.6
JAM2	ENST00000460679.5	n.260-2092G>A		intron_variant		3		ENSP00000436801.1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20337 AN: 152030 Hom.: 1737 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0827

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0869

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.0806

Gnomad OTH AF: 0.129

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

GnomAD4 genome AF: 0.134 AC: 20359 AN: 152148 Hom.: 1740 Cov.: 32 AF XY: 0.134 AC XY: 9955 AN XY: 74370

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.0827

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0869

Gnomad4 NFE AF: 0.0805

Gnomad4 OTH AF: 0.130

Alfa AF: 0.104 Hom.: 220

Bravo AF: 0.142

Asia WGS AF: 0.237 AC: 821 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.56

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: rs2051180; hg19: chr21-27068897;