Variant chr21-25683938-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.123A>G(p.Val41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,600,512 control chromosomes in the GnomAD database, including 8,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 702 hom., cov: 32)

Exomes 𝑓: 0.093 ( 7600 hom. )

Consequence

JAM2
NM_021219.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.773

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 21-25683938-A-G is Benign according to our data. Variant chr21-25683938-A-G is described in ClinVar as [Benign]. Clinvar id is 1259131.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.773 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
JAM2	NM_021219.4 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/10	ENST00000480456.6
JAM2	NM_001270408.2 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/10
JAM2	NM_001270407.2 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/9
JAM2	NR_072999.2 linkuse as main transcript	n.687A>G		non_coding_transcript_exon_variant	2/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JAM2	ENST00000480456.6 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/10	1	NM_021219.4	P1	P57087-1
JAM2	ENST00000400532.5 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/10	1			P57087-3
JAM2	ENST00000312957.9 linkuse as main transcript	c.123A>G	p.Val41=	synonymous_variant	2/9	2			P57087-2

Frequencies

GnomAD3 genomes

AF:

0.0821

AC:

12497

AN:

152186

Hom.:

704

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0393

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.116

Gnomad ASJ

AF:

0.0796

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.0864

Gnomad MID

AF:

0.0759

Gnomad NFE

AF:

0.0798

Gnomad OTH

AF:

0.0975

GnomAD3 exomes

AF:

0.109

AC:

26965

AN:

247760

Hom.:

1980

AF XY:

0.108

AC XY:

14561

AN XY:

134516

show subpopulations

Gnomad AFR exome

AF:

0.0389

Gnomad AMR exome

AF:

0.146

Gnomad ASJ exome

AF:

0.0719

Gnomad EAS exome

AF:

0.295

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.0935

Gnomad NFE exome

AF:

0.0778

Gnomad OTH exome

AF:

0.0916

GnomAD4 exome

AF:

0.0931

AC:

134777

AN:

1448208

Hom.:

7600

Cov.:

AF XY:

0.0943

AC XY:

68049

AN XY:

721336

show subpopulations

Gnomad4 AFR exome

AF:

0.0330

Gnomad4 AMR exome

AF:

0.141

Gnomad4 ASJ exome

AF:

0.0697

Gnomad4 EAS exome

AF:

0.295

Gnomad4 SAS exome

AF:

0.136

Gnomad4 FIN exome

AF:

0.0906

Gnomad4 NFE exome

AF:

0.0828

Gnomad4 OTH exome

AF:

0.0987

GnomAD4 genome

AF:

0.0820

AC:

12495

AN:

152304

Hom.:

702

Cov.:

AF XY:

0.0844

AC XY:

6289

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0392

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.0796

Gnomad4 EAS

AF:

0.297

Gnomad4 SAS

AF:

0.146

Gnomad4 FIN

AF:

0.0864

Gnomad4 NFE

AF:

0.0798

Gnomad4 OTH

AF:

0.0989

Alfa

AF:

0.0811

Hom.:

399

Bravo

AF:

0.0837

Asia WGS

AF:

0.216

AC:

749

AN:

3478

EpiCase

AF:

0.0814

EpiControl

AF:

0.0814

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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

-0.53

CADD

Benign

8.3

DANN

Benign

0.73

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