21-25686077-A-T

Variant names:

• chr21-25686077-A-T
• rs7284014
• NM_021219.4:c.133+2129A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021219.4(JAM2):​c.133+2129A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0400
• Publications: 2 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM2	NM_021219.4	c.133+2129A>T		intron_variant	Intron 2 of 9	ENST00000480456.6	NP_067042.1
JAM2	NM_001270408.2	c.133+2129A>T		intron_variant	Intron 2 of 9		NP_001257337.1
JAM2	NM_001270407.2	c.133+2129A>T		intron_variant	Intron 2 of 8		NP_001257336.1
JAM2	NR_072999.2	n.697+2129A>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+2129A>T		intron_variant	Intron 2 of 9	1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.133+2129A>T		intron_variant	Intron 2 of 9	1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.133+2129A>T		intron_variant	Intron 2 of 8	2		ENSP00000318416.6

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 698

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.68
PhyloP100		0.040

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: rs7284014; hg19: chr21-27058389;