21-25702222-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 4P and 3B. PM1PM2BP4_ModerateBS1_Supporting
The NM_021219.4(JAM2):c.650G>A(p.Arg217His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000282 in 1,597,694 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021219.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
JAM2 | NM_021219.4 | c.650G>A | p.Arg217His | missense_variant | 6/10 | ENST00000480456.6 | |
LOC124905002 | XR_007067827.1 | n.2842-5388C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
JAM2 | ENST00000480456.6 | c.650G>A | p.Arg217His | missense_variant | 6/10 | 1 | NM_021219.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000116 AC: 29AN: 249444Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135332
GnomAD4 exome AF: 0.0000297 AC: 43AN: 1445416Hom.: 0 Cov.: 29 AF XY: 0.0000223 AC XY: 16AN XY: 717740
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74454
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.650G>A (p.R217H) alteration is located in exon 6 (coding exon 6) of the JAM2 gene. This alteration results from a G to A substitution at nucleotide position 650, causing the arginine (R) at amino acid position 217 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at