chr21-25683787-C-A

Position:

• chr21-25683787-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021219.4(JAM2):​c.68-96C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 850,722 control chromosomes in the GnomAD database, including 65,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (11726 hom., cov: 32)
  • Exomes 𝑓: 0.39 (54185 hom.)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.339

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 21-25683787-C-A is Benign according to our data. Variant chr21-25683787-C-A is described in ClinVar as [Benign]. Clinvar id is 1278533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JAM2	NM_021219.4	c.68-96C>A		intron_variant		ENST00000480456.6
JAM2	NM_001270407.2	c.68-96C>A		intron_variant
JAM2	NM_001270408.2	c.68-96C>A		intron_variant
JAM2	NR_072999.2	n.632-96C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAM2	ENST00000480456.6	c.68-96C>A		intron_variant		1	NM_021219.4	P1
JAM2	ENST00000400532.5	c.68-96C>A		intron_variant		1
JAM2	ENST00000312957.9	c.68-96C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59234 AN: 151838 Hom.: 11708 Cov.: 32

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.397

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.389 AC: 271508 AN: 698764 Hom.: 54185 AF XY: 0.395 AC XY: 145284 AN XY: 367828

Gnomad4 AFR exome AF: 0.440

Gnomad4 AMR exome AF: 0.365

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.531

Gnomad4 FIN exome AF: 0.365

Gnomad4 NFE exome AF: 0.385

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.390 AC: 59281 AN: 151958 Hom.: 11726 Cov.: 32 AF XY: 0.391 AC XY: 29058 AN XY: 74274

Gnomad4 AFR AF: 0.432

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.521

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.349

Alfa AF: 0.376 Hom.: 14210

Bravo AF: 0.388

Asia WGS AF: 0.382 AC: 1329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.0
DANN	Benign	0.32

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: rs2829863; hg19: chr21-27056099; COSMIC: COSV57256433;