21-25714732-T-C

Variant names:

• chr21-25714732-T-C
• rs2829877
• NM_021219.4:c.*60T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_021219.4(JAM2):​c.*60T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.086 in 1,125,272 control chromosomes in the GnomAD database, including 4,556 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.093 (720 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3836 hom.)
• Consequence: JAM2 NM_021219.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.293
• Publications: 7 publications found

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, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• bilateral striopallidodentate calcinosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

LOC124905002 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 21-25714732-T-C is Benign according to our data. Variant chr21-25714732-T-C is described in ClinVar as Benign. ClinVar VariationId is 1294897.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAM2	NM_021219.4	c.*60T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000480456.6	NP_067042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.*60T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_021219.4	ENSP00000420419.1

Frequencies

GnomAD3 genomes AF: 0.0927 AC: 14101 AN: 152056 Hom.: 713 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0802

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0347

Gnomad SAS AF: 0.0986

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.0857

Gnomad OTH AF: 0.0872

GnomAD4 exome AF: 0.0849 AC: 82618 AN: 973098 Hom.: 3836 Cov.: 13 AF XY: 0.0847 AC XY: 42016 AN XY: 495934

African (AFR) AF: 0.116 AC: 2245 AN: 19316

American (AMR) AF: 0.0969 AC: 2069 AN: 21358

Ashkenazi Jewish (ASJ) AF: 0.0931 AC: 1709 AN: 18356

East Asian (EAS) AF: 0.0248 AC: 771 AN: 31064

South Asian (SAS) AF: 0.0916 AC: 4898 AN: 53494

European-Finnish (FIN) AF: 0.0954 AC: 4610 AN: 48338

Middle Eastern (MID) AF: 0.131 AC: 599 AN: 4584

European-Non Finnish (NFE) AF: 0.0846 AC: 62159 AN: 734364

Other (OTH) AF: 0.0843 AC: 3558 AN: 42224

GnomAD4 genome AF: 0.0928 AC: 14128 AN: 152174 Hom.: 720 Cov.: 32 AF XY: 0.0946 AC XY: 7039 AN XY: 74414

African (AFR) AF: 0.115 AC: 4794 AN: 41508

American (AMR) AF: 0.0800 AC: 1222 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.0347 AC: 180 AN: 5180

South Asian (SAS) AF: 0.0987 AC: 476 AN: 4824

European-Finnish (FIN) AF: 0.0980 AC: 1039 AN: 10598

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0857 AC: 5829 AN: 68000

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0891 Hom.: 373

Bravo AF: 0.0914

Asia WGS AF: 0.0840 AC: 293 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.74
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2829877; hg19: chr21-27087044; COSMIC: COSV57256924; COSMIC: COSV57256924;