21-25639776-C-G

Variant names:

• chr21-25639776-C-G
• rs118115569
• NM_021219.4:c.-46C>G

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.-46C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000157 in 1,274,426 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: JAM2 NM_021219.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.454
• Publications: 4 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: 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=-0.73).

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.-46C>G		5_prime_UTR	Exon 1 of 10	NP_067042.1	P57087-1
	JAM2	NM_001270408.2		c.-46C>G		5_prime_UTR	Exon 1 of 10	NP_001257337.1	P57087-3
	JAM2	NM_001270407.2		c.-46C>G		5_prime_UTR	Exon 1 of 9	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.-46C>G		5_prime_UTR	Exon 1 of 10	ENSP00000420419.1	P57087-1
	JAM2	ENST00000400532.5	TSL:1	c.-46C>G		5_prime_UTR	Exon 1 of 10	ENSP00000383376.1	P57087-3
	JAM2	ENST00000948521.1		c.-46C>G		5_prime_UTR	Exon 1 of 11	ENSP00000618580.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 138168 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000157 AC: 2 AN: 1274426 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 633972

African (AFR) AF: 0.00 AC: 0 AN: 28746

American (AMR) AF: 0.00 AC: 0 AN: 33756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23644

East Asian (EAS) AF: 0.00 AC: 0 AN: 34976

South Asian (SAS) AF: 0.00 AC: 0 AN: 75450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4812

European-Non Finnish (NFE) AF: 0.00000204 AC: 2 AN: 981050

Other (OTH) AF: 0.00 AC: 0 AN: 53752

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.80
PhyloP100		0.45
PromoterAI		-0.048	Neutral

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: rs118115569; hg19: chr21-27012088;