rs2829841

Variant names:

• chr21-25650710-C-T
• rs2829841
• NM_021219.4:c.67+10822C>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.67+10822C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 151,898 control chromosomes in the GnomAD database, including 4,056 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 0.21 (4056 hom., cov: 32)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.630
• Publications: 16 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

ENSG00000287109 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM2	NM_021219.4	c.67+10822C>T		intron_variant	Intron 1 of 9	ENST00000480456.6	NP_067042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.67+10822C>T		intron_variant	Intron 1 of 9	1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.67+10822C>T		intron_variant	Intron 1 of 9	1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.67+10822C>T		intron_variant	Intron 1 of 8	2		ENSP00000318416.6
ENSG00000287109	ENST00000659278.1	n.2570+1392G>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.213 AC: 32340 AN: 151780 Hom.: 4036 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.252

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.0927

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.213 AC: 32408 AN: 151898 Hom.: 4056 Cov.: 32 AF XY: 0.218 AC XY: 16202 AN XY: 74232

African (AFR) AF: 0.343 AC: 14192 AN: 41424

American (AMR) AF: 0.205 AC: 3133 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 321 AN: 3462

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5166

South Asian (SAS) AF: 0.322 AC: 1548 AN: 4814

European-Finnish (FIN) AF: 0.173 AC: 1817 AN: 10516

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9329 AN: 67932

Other (OTH) AF: 0.190 AC: 401 AN: 2106

Alfa AF: 0.162 Hom.: 7445

Bravo AF: 0.217

Asia WGS AF: 0.284 AC: 988 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.42
PhyloP100		-0.63
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: rs2829841; hg19: chr21-27023022;