NM_021219.4:c.21C>A

Variant names:

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.21C>A(p.His7Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,590,384 control chromosomes in the GnomAD database, including 125 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H7R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.017 ( 66 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 59 hom. )

Consequence

JAM2
NM_021219.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.42

Publications

2 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 (MetaRNN=0.0020769238).

BP6

Variant 21-25639842-C-A is Benign according to our data. Variant chr21-25639842-C-A is described in ClinVar as Benign. ClinVar VariationId is 1276642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0569 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	HGVSp	Effect	Exon Rank	Protein	UniProt
JAM2	NM_021219.4	MANE Select	c.21C>A	p.His7Gln	missense	Exon 1 of 10	NP_067042.1	P57087-1
JAM2	NM_001270408.2		c.21C>A	p.His7Gln	missense	Exon 1 of 10	NP_001257337.1	P57087-3
JAM2	NM_001270407.2		c.21C>A	p.His7Gln	missense	Exon 1 of 9	NP_001257336.1	P57087-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
JAM2	ENST00000480456.6	TSL:1 MANE Select	c.21C>A	p.His7Gln	missense	Exon 1 of 10	ENSP00000420419.1	P57087-1
JAM2	ENST00000400532.5	TSL:1	c.21C>A	p.His7Gln	missense	Exon 1 of 10	ENSP00000383376.1	P57087-3
JAM2	ENST00000948521.1		c.21C>A	p.His7Gln	missense	Exon 1 of 11	ENSP00000618580.1

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2578

AN:

151890

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0590

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.00817

GnomAD2 exomes

AF:

0.00385

AC:

800

AN:

207972

AF XY:

0.00293

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.00219

Gnomad ASJ exome

AF:

0.000868

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000650

Gnomad OTH exome

AF:

0.000774

GnomAD4 exome

AF:

0.00171

AC:

2453

AN:

1438374

Hom.:

Cov.:

AF XY:

0.00142

AC XY:

1010

AN XY:

713582

show subpopulations

African (AFR)

AF:

0.0598

AC:

1977

AN:

33054

American (AMR)

AF:

0.00259

AC:

108

AN:

41630

Ashkenazi Jewish (ASJ)

AF:

0.000820

AC:

AN:

25614

East Asian (EAS)

AF:

0.00

AC:

AN:

38772

South Asian (SAS)

AF:

0.000170

AC:

AN:

82370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49202

Middle Eastern (MID)

AF:

0.00246

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0000508

AC:

AN:

1102526

Other (OTH)

AF:

0.00442

AC:

263

AN:

59506

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

105

210

314

419

524

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

204

272

340

<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:

0.0170

AC:

2581

AN:

152010

Hom.:

Cov.:

AF XY:

0.0160

AC XY:

1189

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.0589

AC:

2440

AN:

41446

American (AMR)

AF:

0.00693

AC:

106

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5130

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000221

AC:

AN:

67960

Other (OTH)

AF:

0.00807

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00474

Hom.:

Bravo

AF:

0.0190

ESP6500AA

AF:

0.0454

AC:

179

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.00429

AC:

514

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

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.029

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.38

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

PhyloP100

1.4

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.69

REVEL

Benign

0.035

Sift

Benign

0.44

Sift4G

Benign

0.23

Polyphen

0.0020

Vest4

0.17

MutPred

0.40

Gain of helix (P = 0.0325)

MVP

0.48

MPC

0.23

ClinPred

0.019

GERP RS

3.2

Varity_R

0.057

gMVP

0.56

Mutation Taster

=99/1

polymorphism

(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