Variant chr1-119912963-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024408.4(NOTCH2):c.*2343A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 233,268 control chromosomes in the GnomAD database, including 3,901 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.17 ( 3270 hom., cov: 33)

Exomes 𝑓: 0.10 ( 631 hom. )

Consequence

NOTCH2
NM_024408.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.26

Variant links:

Genes affected

NOTCH2 (HGNC:7882): (notch receptor 2) This gene encodes a member of the Notch family. Members of this Type 1 transmembrane protein family share structural characteristics including an extracellular domain consisting of multiple epidermal growth factor-like (EGF) repeats, and an intracellular domain consisting of multiple, different domain types. Notch family members play a role in a variety of developmental processes by controlling cell fate decisions. The Notch signaling network is an evolutionarily conserved intercellular signaling pathway which regulates interactions between physically adjacent cells. In Drosophilia, notch interaction with its cell-bound ligands (delta, serrate) establishes an intercellular signaling pathway that plays a key role in development. Homologues of the notch-ligands have also been identified in human, but precise interactions between these ligands and the human notch homologues remain to be determined. This protein is cleaved in the trans-Golgi network, and presented on the cell surface as a heterodimer. This protein functions as a receptor for membrane bound ligands, and may play a role in vascular, renal and hepatic development. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

NOTCH2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.96).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NOTCH2	NM_024408.4 linkuse as main transcript	c.*2343A>G		3_prime_UTR_variant	34/34	ENST00000256646.7	NP_077719.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NOTCH2	ENST00000256646.7 linkuse as main transcript	c.*2343A>G		3_prime_UTR_variant	34/34	1	NM_024408.4	ENSP00000256646	P1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26446

AN:

152034

Hom.:

3258

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0833

Gnomad EAS

AF:

0.0320

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.135

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.159

GnomAD4 exome

AF:

0.104

AC:

8432

AN:

81116

Hom.:

631

Cov.:

AF XY:

0.101

AC XY:

3787

AN XY:

37326

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.115

Gnomad4 ASJ exome

AF:

0.0699

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.178

Gnomad4 FIN exome

AF:

0.137

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.174

AC:

26480

AN:

152152

Hom.:

3270

Cov.:

AF XY:

0.173

AC XY:

12894

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.346

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0833

Gnomad4 EAS

AF:

0.0317

Gnomad4 SAS

AF:

0.190

Gnomad4 FIN

AF:

0.135

Gnomad4 NFE

AF:

0.107

Gnomad4 OTH

AF:

0.158

Alfa

AF:

0.114

Hom.:

1144

Bravo

AF:

0.177

Asia WGS

AF:

0.166

AC:

577

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.0040

DANN

Benign

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over