rs11087972

Variant names:

• chr21-25686414-C-T
• rs11087972
• NM_021219.4:c.133+2466C>T

Variant summary

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

The NM_021219.4(JAM2):​c.133+2466C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0819 in 151,804 control chromosomes in the GnomAD database, including 699 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 0.082 (699 hom., cov: 33)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889
• 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM2	NM_021219.4	c.133+2466C>T		intron_variant	Intron 2 of 9	ENST00000480456.6	NP_067042.1
JAM2	NM_001270408.2	c.133+2466C>T		intron_variant	Intron 2 of 9		NP_001257337.1
JAM2	NM_001270407.2	c.133+2466C>T		intron_variant	Intron 2 of 8		NP_001257336.1
JAM2	NR_072999.2	n.697+2466C>T		intron_variant	Intron 2 of 9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.133+2466C>T		intron_variant	Intron 2 of 9	1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.133+2466C>T		intron_variant	Intron 2 of 9	1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.133+2466C>T		intron_variant	Intron 2 of 8	2		ENSP00000318416.6

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12435 AN: 151686 Hom.: 701 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.0873

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0794

Gnomad OTH AF: 0.0960

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

GnomAD4 genome AF: 0.0819 AC: 12435 AN: 151804 Hom.: 699 Cov.: 33 AF XY: 0.0844 AC XY: 6264 AN XY: 74186

African (AFR) AF: 0.0394 AC: 1627 AN: 41338

American (AMR) AF: 0.114 AC: 1742 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1544 AN: 5168

South Asian (SAS) AF: 0.147 AC: 702 AN: 4782

European-Finnish (FIN) AF: 0.0873 AC: 921 AN: 10546

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0794 AC: 5395 AN: 67944

Other (OTH) AF: 0.0973 AC: 205 AN: 2106

Alfa AF: 0.0896 Hom.: 317

Bravo AF: 0.0832

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.7
DANN	Benign	0.67
PhyloP100		0.89
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: rs11087972; hg19: chr21-27058726;