Genetic Variant NM_021219.4:c.68-96C>A (chr21-25683787-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.339

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

basal ganglia calcification, idiopathic, 8, autosomal recessive
Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
bilateral striopallidodentate calcinosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

JAM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021219.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JAM2	NM_021219.4	MANE Select	c.68-96C>A	intron	N/A	NP_067042.1	P57087-1
JAM2	NM_001270408.2		c.68-96C>A	intron	N/A	NP_001257337.1	P57087-3
JAM2	NM_001270407.2		c.68-96C>A	intron	N/A	NP_001257336.1	P57087-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
JAM2	ENST00000480456.6	TSL:1 MANE Select	c.68-96C>A	intron	N/A	ENSP00000420419.1	P57087-1
JAM2	ENST00000400532.5	TSL:1	c.68-96C>A	intron	N/A	ENSP00000383376.1	P57087-3
JAM2	ENST00000948521.1		c.113-96C>A	intron	N/A	ENSP00000618580.1

Frequencies

GnomAD3 genomes

AF:

0.390

AC:

59234

AN:

151838

Hom.:

11708

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.440

AC:

6968

AN:

15834

American (AMR)

AF:

0.365

AC:

8256

AN:

22646

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

6279

AN:

19568

East Asian (EAS)

AF:

0.267

AC:

8267

AN:

30942

South Asian (SAS)

AF:

0.531

AC:

29937

AN:

56382

European-Finnish (FIN)

AF:

0.365

AC:

16711

AN:

45826

Middle Eastern (MID)

AF:

0.428

AC:

1342

AN:

3132

European-Non Finnish (NFE)

AF:

0.385

AC:

180846

AN:

470066

Other (OTH)

AF:

0.375

AC:

12902

AN:

34368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7857

15714

23572

31429

39286

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3390

6780

10170

13560

16950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.390

AC:

59281

AN:

151958

Hom.:

11726

Cov.:

AF XY:

0.391

AC XY:

29058

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.432

AC:

17926

AN:

41468

American (AMR)

AF:

0.370

AC:

5645

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1091

AN:

3470

East Asian (EAS)

AF:

0.271

AC:

1399

AN:

5170

South Asian (SAS)

AF:

0.521

AC:

2502

AN:

4804

European-Finnish (FIN)

AF:

0.367

AC:

3871

AN:

10552

Middle Eastern (MID)

AF:

0.386

AC:

112

AN:

290

European-Non Finnish (NFE)

AF:

0.377

AC:

25589

AN:

67922

Other (OTH)

AF:

0.349

AC:

737

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1831

3662

5494

7325

9156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.377

Hom.:

16996

Bravo

AF:

0.388

Asia WGS

AF:

0.382

AC:

1329

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.0

(source)

DANN

Benign

0.32

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over