rs7284014

chr21-25686077-A-Gchr21-25686077-A-T

Variant summary

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

The NM_021219.4(JAM2):c.133+2129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,120 control chromosomes in the GnomAD database, including 4,933 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 0.25 (4933 hom., cov: 32)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAM2	NM_021219.4	c.133+2129A>G		intron_variant		ENST00000480456.6
JAM2	NM_001270407.2	c.133+2129A>G		intron_variant
JAM2	NM_001270408.2	c.133+2129A>G		intron_variant
JAM2	NR_072999.2	n.697+2129A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAM2	ENST00000480456.6	c.133+2129A>G		intron_variant		1	NM_021219.4	P1
JAM2	ENST00000400532.5	c.133+2129A>G		intron_variant		1
JAM2	ENST00000312957.9	c.133+2129A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37434 AN: 152002 Hom.: 4924 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.0642

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.246 AC: 37469 AN: 152120 Hom.: 4933 Cov.: 32 AF XY: 0.243 AC XY: 18086 AN XY: 74368

Gnomad4 AFR AF: 0.329

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.0638

Gnomad4 SAS AF: 0.306

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.224

Alfa AF: 0.225 Hom.: 651

Bravo AF: 0.247

Asia WGS AF: 0.206 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.73

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: rs7284014; hg19: chr21-27058389;