chr14-105142709-C-T
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002226.5(JAG2):c.3703G>A(p.Ala1235Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000517 in 1,601,026 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 3 hom., cov: 33)
Exomes 𝑓: 0.00032 ( 3 hom. )
Consequence
JAG2
NM_002226.5 missense
NM_002226.5 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 0.724
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 Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0060788095).
BP6
Variant 14-105142709-C-T is Benign according to our data. Variant chr14-105142709-C-T is described in ClinVar as [Benign]. Clinvar id is 725844.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
JAG2 | NM_002226.5 | c.3703G>A | p.Ala1235Thr | missense_variant | 26/26 | ENST00000331782.8 | NP_002217.3 | |
JAG2 | NM_145159.3 | c.3589G>A | p.Ala1197Thr | missense_variant | 25/25 | NP_660142.1 | ||
JAG2 | XM_047431352.1 | c.3361G>A | p.Ala1121Thr | missense_variant | 25/25 | XP_047287308.1 | ||
JAG2 | XM_047431353.1 | c.3247G>A | p.Ala1083Thr | missense_variant | 24/24 | XP_047287309.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
JAG2 | ENST00000331782.8 | c.3703G>A | p.Ala1235Thr | missense_variant | 26/26 | 1 | NM_002226.5 | ENSP00000328169 | P1 | |
JAG2 | ENST00000347004.2 | c.3589G>A | p.Ala1197Thr | missense_variant | 25/25 | 1 | ENSP00000328566 | |||
JAG2 | ENST00000546616.1 | n.1321G>A | non_coding_transcript_exon_variant | 7/7 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00237 AC: 361AN: 152202Hom.: 3 Cov.: 33
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GnomAD3 exomes AF: 0.000719 AC: 160AN: 222602Hom.: 1 AF XY: 0.000457 AC XY: 56AN XY: 122408
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GnomAD4 exome AF: 0.000322 AC: 466AN: 1448706Hom.: 3 Cov.: 30 AF XY: 0.000293 AC XY: 211AN XY: 719590
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GnomAD4 genome AF: 0.00238 AC: 362AN: 152320Hom.: 3 Cov.: 33 AF XY: 0.00224 AC XY: 167AN XY: 74474
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 24, 2018 | - - |
JAG2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 16, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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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