chr21-25693548-T-C

Position:

• chr21-25693548-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.63

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4	c.242-208T>C		intron_variant		ENST00000480456.6	NP_067042.1
JAM2	NM_001270407.2	c.134-208T>C		intron_variant			NP_001257336.1
JAM2	NM_001270408.2	c.242-208T>C		intron_variant			NP_001257337.1
JAM2	NR_072999.2	n.806-208T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.242-208T>C		intron_variant		1	NM_021219.4	ENSP00000420419	P1
JAM2	ENST00000400532.5	c.242-208T>C		intron_variant		1		ENSP00000383376
JAM2	ENST00000312957.9	c.134-208T>C		intron_variant		2		ENSP00000318416
JAM2	ENST00000460679.5	c.109-208T>C		intron_variant, NMD_transcript_variant		3		ENSP00000436801

Frequencies

GnomAD3 genomes AF: 0.512 AC: 77765 AN: 151988 Hom.: 20377 Cov.: 33

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.: 33 AF XY: 0.514 AC XY: 38188 AN XY: 74354

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.502

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.669

Gnomad4 FIN AF: 0.457

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.474

Alfa AF: 0.315 Hom.: 716

Bravo AF: 0.515

Asia WGS AF: 0.612 AC: 2127 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.13
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs9984260; hg19: chr21-27065860;