14-105142807-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002226.5(JAG2):c.3605C>T(p.Thr1202Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000931 in 1,610,690 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Consequence
JAG2
NM_002226.5 missense
NM_002226.5 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 3.87
Genes affected
JAG2 (HGNC:6189): (jagged canonical Notch ligand 2) The Notch signaling pathway is an intercellular signaling mechanism that is essential for proper embryonic development. Members of the Notch gene family encode transmembrane receptors that are critical for various cell fate decisions. The protein encoded by this gene is one of several ligands that activate Notch and related receptors. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
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=0.32214415).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JAG2 | NM_002226.5 | c.3605C>T | p.Thr1202Ile | missense_variant | 26/26 | ENST00000331782.8 | NP_002217.3 | |
JAG2 | NM_145159.3 | c.3491C>T | p.Thr1164Ile | missense_variant | 25/25 | NP_660142.1 | ||
JAG2 | XM_047431352.1 | c.3263C>T | p.Thr1088Ile | missense_variant | 25/25 | XP_047287308.1 | ||
JAG2 | XM_047431353.1 | c.3149C>T | p.Thr1050Ile | missense_variant | 24/24 | XP_047287309.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JAG2 | ENST00000331782.8 | c.3605C>T | p.Thr1202Ile | missense_variant | 26/26 | 1 | NM_002226.5 | ENSP00000328169 | P1 | |
JAG2 | ENST00000347004.2 | c.3491C>T | p.Thr1164Ile | missense_variant | 25/25 | 1 | ENSP00000328566 | |||
JAG2 | ENST00000546616.1 | n.1223C>T | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152270Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000818 AC: 2AN: 244582Hom.: 0 AF XY: 0.00000751 AC XY: 1AN XY: 133162
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GnomAD4 exome AF: 0.00000891 AC: 13AN: 1458420Hom.: 0 Cov.: 30 AF XY: 0.00000551 AC XY: 4AN XY: 725370
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152270Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74392
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 10, 2022 | The c.3605C>T (p.T1202I) alteration is located in exon 26 (coding exon 26) of the JAG2 gene. This alteration results from a C to T substitution at nucleotide position 3605, causing the threonine (T) at amino acid position 1202 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N
REVEL
Uncertain
Sift
Benign
D;T
Sift4G
Benign
T;T
Polyphen
P;P
Vest4
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at