Variant chr21-25698693-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_021219.4(JAM2):c.411A>G(p.Pro137=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 1,613,946 control chromosomes in the GnomAD database, including 244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 121 hom. )

Consequence

JAM2
NM_021219.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.30

Variant links:

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 links:

LOC124905002 (HGNC:):

LOC124905002 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 21-25698693-A-G is Benign according to our data. Variant chr21-25698693-A-G is described in ClinVar as [Benign]. Clinvar id is 777613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.3 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4 linkuse as main transcript	c.411A>G	p.Pro137=	synonymous_variant	5/10	ENST00000480456.6	NP_067042.1
LOC124905002	XR_007067827.1 linkuse as main transcript	n.2842-1859T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6 linkuse as main transcript	c.411A>G	p.Pro137=	synonymous_variant	5/10	1	NM_021219.4	ENSP00000420419	P1	P57087-1
JAM2	ENST00000400532.5 linkuse as main transcript	c.411A>G	p.Pro137=	synonymous_variant	5/10	1		ENSP00000383376		P57087-3
JAM2	ENST00000312957.9 linkuse as main transcript	c.303A>G	p.Pro101=	synonymous_variant	4/9	2		ENSP00000318416		P57087-2
JAM2	ENST00000460679.5 linkuse as main transcript	c.279A>G	p.Pro93=	synonymous_variant, NMD_transcript_variant	3/9	3		ENSP00000436801

Frequencies

GnomAD3 genomes

AF:

0.0221

AC:

3356

AN:

152168

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0760

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00785

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.000588

Gnomad OTH

AF:

0.0134

GnomAD3 exomes

AF:

0.00602

AC:

1501

AN:

249226

Hom.:

AF XY:

0.00475

AC XY:

643

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.0808

Gnomad AMR exome

AF:

0.00400

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000262

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000425

Gnomad OTH exome

AF:

0.00264

GnomAD4 exome

AF:

0.00259

AC:

3793

AN:

1461660

Hom.:

121

Cov.:

AF XY:

0.00224

AC XY:

1629

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.0780

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.00337

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000255

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000371

Gnomad4 OTH exome

AF:

0.00677

GnomAD4 genome

AF:

0.0221

AC:

3364

AN:

152286

Hom.:

123

Cov.:

AF XY:

0.0208

AC XY:

1551

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0759

Gnomad4 AMR

AF:

0.00784

Gnomad4 ASJ

AF:

0.00317

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000588

Gnomad4 OTH

AF:

0.0133

Alfa

AF:

0.0148

Hom.:

Bravo

AF:

0.0259

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.000890

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.1

DANN

Benign

0.67

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over