21-25693607-A-G

Position:

• chr21-25693607-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021219.4(JAM2):​c.242-149A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 658,694 control chromosomes in the GnomAD database, including 173 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.022 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (49 hom.)
• Consequence: JAM2 NM_021219.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.30

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-25693607-A-G is Benign according to our data. Variant chr21-25693607-A-G is described in ClinVar as [Benign]. Clinvar id is 1227361.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4	c.242-149A>G		intron_variant		ENST00000480456.6	NP_067042.1
JAM2	NM_001270407.2	c.134-149A>G		intron_variant			NP_001257336.1
JAM2	NM_001270408.2	c.242-149A>G		intron_variant			NP_001257337.1
JAM2	NR_072999.2	n.806-149A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.242-149A>G		intron_variant		1	NM_021219.4	ENSP00000420419	P1
JAM2	ENST00000400532.5	c.242-149A>G		intron_variant		1		ENSP00000383376
JAM2	ENST00000312957.9	c.134-149A>G		intron_variant		2		ENSP00000318416
JAM2	ENST00000460679.5	c.109-149A>G		intron_variant, NMD_transcript_variant		3		ENSP00000436801

Frequencies

GnomAD3 genomes AF: 0.0216 AC: 3293 AN: 152186 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0753

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00799

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.00255 AC: 1289 AN: 506390 Hom.: 49 AF XY: 0.00216 AC XY: 570 AN XY: 263546

Gnomad4 AFR exome AF: 0.0745

Gnomad4 AMR exome AF: 0.00458

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000428

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000202

Gnomad4 OTH exome AF: 0.00642

GnomAD4 genome AF: 0.0217 AC: 3309 AN: 152304 Hom.: 124 Cov.: 32 AF XY: 0.0206 AC XY: 1533 AN XY: 74478

Gnomad4 AFR AF: 0.0755

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.0172 Hom.: 5

Bravo AF: 0.0243

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 13, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	12
DANN	Benign	0.76

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: rs61140678; hg19: chr21-27065919;