21-25639886-GC-AT

Variant names:

• chr21-25639886-GC-AT
• NM_021219.4:c.65_66delGCinsAT
• JAM2 p.Gly22Asp

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_021219.4(JAM2):​c.65_66delGCinsAT​(p.Gly22Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAM2 NM_021219.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 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, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM2	NM_021219.4	MANE Select	c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	NP_067042.1	P57087-1
	JAM2	NM_001270408.2		c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	NP_001257337.1	P57087-3
	JAM2	NM_001270407.2		c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	NP_001257336.1	P57087-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JAM2	ENST00000480456.6	TSL:1 MANE Select	c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	ENSP00000420419.1	P57087-1
	JAM2	ENST00000400532.5	TSL:1	c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	ENSP00000383376.1	P57087-3
	JAM2	ENST00000948521.1		c.65_66delGCinsAT	p.Gly22Asp	missense splice_region	N/A	ENSP00000618580.1

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-27012198;