NM_021219.4:c.865-1128C>T

Variant names:

• chr21-25713512-C-T
• rs2829876
• NM_021219.4:c.865-1128C>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.865-1128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 138,194 control chromosomes in the GnomAD database, including 794 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 0.11 (794 hom., cov: 29)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 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

LOC124905002 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021219.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM2	NM_021219.4	MANE Select	c.865-1128C>T		intron	N/A	NP_067042.1
	JAM2	NM_001270408.2		c.865-719C>T		intron	N/A	NP_001257337.1
	JAM2	NM_001270407.2		c.757-1128C>T		intron	N/A	NP_001257336.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM2	ENST00000480456.6	TSL:1 MANE Select	c.865-1128C>T		intron	N/A	ENSP00000420419.1
	JAM2	ENST00000400532.5	TSL:1	c.865-719C>T		intron	N/A	ENSP00000383376.1
	JAM2	ENST00000312957.9	TSL:2	c.757-1128C>T		intron	N/A	ENSP00000318416.6

Frequencies

GnomAD3 genomes AF: 0.106 AC: 14589 AN: 138068 Hom.: 784 Cov.: 29

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0148

Gnomad AMR AF: 0.0955

Gnomad ASJ AF: 0.0969

Gnomad EAS AF: 0.0405

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.159

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0983

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

GnomAD4 genome AF: 0.106 AC: 14628 AN: 138194 Hom.: 794 Cov.: 29 AF XY: 0.109 AC XY: 7212 AN XY: 66228

African (AFR) AF: 0.146 AC: 5398 AN: 36896

American (AMR) AF: 0.0953 AC: 1231 AN: 12918

Ashkenazi Jewish (ASJ) AF: 0.0969 AC: 328 AN: 3384

East Asian (EAS) AF: 0.0405 AC: 176 AN: 4342

South Asian (SAS) AF: 0.108 AC: 455 AN: 4202

European-Finnish (FIN) AF: 0.126 AC: 990 AN: 7864

Middle Eastern (MID) AF: 0.156 AC: 44 AN: 282

European-Non Finnish (NFE) AF: 0.0884 AC: 5791 AN: 65522

Other (OTH) AF: 0.106 AC: 202 AN: 1904

Alfa AF: 0.0913 Hom.: 238

Bravo AF: 0.0976

Asia WGS AF: 0.0870 AC: 303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.51
PhyloP100		-0.17
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: rs2829876; hg19: chr21-27085824;