rs2409148

Variant names:

• chr21-25664879-A-G
• rs2409148
• NM_021219.4:c.68-19004A>G

Variant summary

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

The NM_021219.4(JAM2):​c.68-19004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0551 in 152,302 control chromosomes in the GnomAD database, including 255 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 0.055 (255 hom., cov: 33)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• basal ganglia calcification, idiopathic, 8, autosomal recessive

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM2	NM_021219.4	c.68-19004A>G		intron_variant	Intron 1 of 9	ENST00000480456.6	NP_067042.1
JAM2	NM_001270408.2	c.68-19004A>G		intron_variant	Intron 1 of 9		NP_001257337.1
JAM2	NM_001270407.2	c.68-19004A>G		intron_variant	Intron 1 of 8		NP_001257336.1
JAM2	NR_072999.2	n.632-19004A>G		intron_variant	Intron 1 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.68-19004A>G		intron_variant	Intron 1 of 9	1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.68-19004A>G		intron_variant	Intron 1 of 9	1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.68-19004A>G		intron_variant	Intron 1 of 8	2		ENSP00000318416.6

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8387 AN: 152184 Hom.: 254 Cov.: 33

Gnomad AFR AF: 0.0551

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.0792

Gnomad EAS AF: 0.00962

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0523

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0581

Gnomad OTH AF: 0.0502

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

GnomAD4 genome AF: 0.0551 AC: 8389 AN: 152302 Hom.: 255 Cov.: 33 AF XY: 0.0555 AC XY: 4131 AN XY: 74472

African (AFR) AF: 0.0549 AC: 2283 AN: 41570

American (AMR) AF: 0.0624 AC: 955 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0792 AC: 275 AN: 3472

East Asian (EAS) AF: 0.00965 AC: 50 AN: 5184

South Asian (SAS) AF: 0.0346 AC: 167 AN: 4826

European-Finnish (FIN) AF: 0.0523 AC: 555 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0581 AC: 3953 AN: 68024

Other (OTH) AF: 0.0502 AC: 106 AN: 2112

Alfa AF: 0.0579 Hom.: 436

Bravo AF: 0.0569

Asia WGS AF: 0.0410 AC: 143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		-0.019
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: rs2409148; hg19: chr21-27037191;