Genetic Variant JAM2:c.242-208T>C (chr21-25693548-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_021219.4(JAM2):c.242-208T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.512 in 152,106 control chromosomes in the GnomAD database, including 20,401 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.51 ( 20401 hom., cov: 33)

Consequence

JAM2
NM_021219.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.63

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BP6

Variant 21-25693548-T-C is Benign according to our data. Variant chr21-25693548-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231060.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.649 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.242-208T>C	intron	N/A	NP_067042.1	P57087-1
JAM2	NM_001270408.2		c.242-208T>C	intron	N/A	NP_001257337.1	P57087-3
JAM2	NM_001270407.2		c.134-208T>C	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.242-208T>C	intron	N/A	ENSP00000420419.1	P57087-1
JAM2	ENST00000400532.5	TSL:1	c.242-208T>C	intron	N/A	ENSP00000383376.1	P57087-3
JAM2	ENST00000948521.1		c.287-208T>C	intron	N/A	ENSP00000618580.1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77765

AN:

151988

Hom.:

20377

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.451

Gnomad AMR

AF:

0.501

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.569

Gnomad SAS

AF:

0.669

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.457

Gnomad OTH

AF:

0.476

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.512

AC:

77836

AN:

152106

Hom.:

20401

Cov.:

AF XY:

0.514

AC XY:

38188

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.606

AC:

25164

AN:

41496

American (AMR)

AF:

0.502

AC:

7668

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1386

AN:

3470

East Asian (EAS)

AF:

0.568

AC:

2938

AN:

5172

South Asian (SAS)

AF:

0.669

AC:

3226

AN:

4824

European-Finnish (FIN)

AF:

0.457

AC:

4828

AN:

10574

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.457

AC:

31074

AN:

67970

Other (OTH)

AF:

0.474

AC:

1001

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1932

3865

5797

7730

9662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

698

1396

2094

2792

3490

<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:

0.315

Hom.:

716

Bravo

AF:

0.515

Asia WGS

AF:

0.612

AC:

2127

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.68

PhyloP100

-1.6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over