chr14-105142892-C-A

Variant names:

• chr14-105142892-C-A
• rs148815369
• NM_002226.5:c.3520G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002226.5(JAG2):​c.3520G>T​(p.Val1174Phe) 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: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: JAG2 NM_002226.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.120043874).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
JAG2	NM_002226.5	c.3520G>T	p.Val1174Phe	missense_variant	Exon 26 of 26	ENST00000331782.8	NP_002217.3
JAG2	NM_145159.3	c.3406G>T	p.Val1136Phe	missense_variant	Exon 25 of 25		NP_660142.1
JAG2	XM_047431352.1	c.3178G>T	p.Val1060Phe	missense_variant	Exon 25 of 25		XP_047287308.1
JAG2	XM_047431353.1	c.3064G>T	p.Val1022Phe	missense_variant	Exon 24 of 24		XP_047287309.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
JAG2	ENST00000331782.8	c.3520G>T	p.Val1174Phe	missense_variant	Exon 26 of 26	1	NM_002226.5	ENSP00000328169.3
JAG2	ENST00000347004.2	c.3406G>T	p.Val1136Phe	missense_variant	Exon 25 of 25	1		ENSP00000328566.2
JAG2	ENST00000546616.1	n.1138G>T		non_coding_transcript_exon_variant	Exon 7 of 7	5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1447882 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 719196

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	0.28
DANN	Benign	0.45
DEOGEN2	Benign	0.42	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.63	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	0.69	N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.22
Sift	Benign	0.12	T;T
Sift4G	Benign	0.12	T;T
Polyphen		0.054	B;B
Vest4		0.15
MutPred		0.18		Loss of stability (P = 0.1745);.;
MVP		0.41
MPC		0.46
ClinPred		0.084	T
GERP RS		2.0
Varity_R		0.044
gMVP		0.039

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: rs148815369; hg19: chr14-105609229;