chr21-25689883-A-C

Position:

• chr21-25689883-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021219.4(JAM2):​c.151A>C​(p.Lys51Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: JAM2 NM_021219.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3453358).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JAM2	NM_021219.4	c.151A>C	p.Lys51Gln	missense_variant	3/10	ENST00000480456.6	NP_067042.1
JAM2	NM_001270408.2	c.151A>C	p.Lys51Gln	missense_variant	3/10		NP_001257337.1
JAM2	NM_001270407.2	c.134-3873A>C		intron_variant			NP_001257336.1
JAM2	NR_072999.2	n.715A>C		non_coding_transcript_exon_variant	3/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JAM2	ENST00000480456.6	c.151A>C	p.Lys51Gln	missense_variant	3/10	1	NM_021219.4	ENSP00000420419.1
JAM2	ENST00000400532.5	c.151A>C	p.Lys51Gln	missense_variant	3/10	1		ENSP00000383376.1
JAM2	ENST00000312957.9	c.134-3873A>C		intron_variant		2		ENSP00000318416.6
JAM2	ENST00000460679.5	n.16A>C		non_coding_transcript_exon_variant	1/9	3		ENSP00000436801.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2024

The c.151A>C (p.K51Q) alteration is located in exon 3 (coding exon 3) of the JAM2 gene. This alteration results from a A to C substitution at nucleotide position 151, causing the lysine (K) at amino acid position 51 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.045	T
BayesDel_noAF	Benign	-0.30
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.078	.;T
Eigen	Benign	0.016
Eigen_PC	Benign	-0.067
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L;L
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.23
Sift	Benign	0.33	T;T
Sift4G	Uncertain	0.036	D;T
Polyphen		0.99	.;D
Vest4		0.39
MutPred		0.49		Loss of methylation at K51 (P = 0.0012);Loss of methylation at K51 (P = 0.0012);
MVP		0.83
MPC		0.68
ClinPred		0.94	D
GERP RS		3.8
Varity_R		0.19
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr21-27062195;