chr21-25650710-C-T

Position:

• chr21-25650710-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
JAM2	NM_021219.4	c.67+10822C>T		intron_variant		ENST00000480456.6
LOC124905001	XR_007067826.1	n.2536+1392G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAM2	ENST00000480456.6	c.67+10822C>T		intron_variant		1	NM_021219.4	P1
JAM2	ENST00000400532.5	c.67+10822C>T		intron_variant		1
	ENST00000659278.1	n.2570+1392G>A		intron_variant, non_coding_transcript_variant
JAM2	ENST00000312957.9	c.67+10822C>T		intron_variant		2

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

Gnomad4 AFR AF: 0.343

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.0927

Gnomad4 EAS AF: 0.266

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.137

Gnomad4 OTH AF: 0.190

Alfa AF: 0.151 Hom.: 4090

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2829841; hg19: chr21-27023022;