1-119958328-C-G

Variant summary

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

The NM_024408.4(NOTCH2):​c.2026+1064G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0552 in 152,246 control chromosomes in the GnomAD database, including 302 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 0.055 ( 302 hom., cov: 32)

Consequence

NOTCH2
NM_024408.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.271
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]

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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=-0.83).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
NOTCH2NM_024408.4 linkc.2026+1064G>C intron_variant ENST00000256646.7 NP_077719.2 Q04721Q6IQ50Q9UFD5
NOTCH2NM_001200001.2 linkc.2026+1064G>C intron_variant NP_001186930.1 Q04721Q6IQ50

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
NOTCH2ENST00000256646.7 linkc.2026+1064G>C intron_variant 1 NM_024408.4 ENSP00000256646.2 Q04721
NOTCH2ENST00000479412.2 linkn.2164+1064G>C intron_variant 1
NOTCH2ENST00000640021.1 linkn.*1150+1064G>C intron_variant 5 ENSP00000492223.1 A0A1W2PQQ5

Frequencies

GnomAD3 genomes
AF:
0.0552
AC:
8398
AN:
152128
Hom.:
301
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0455
Gnomad AMI
AF:
0.0592
Gnomad AMR
AF:
0.0492
Gnomad ASJ
AF:
0.0681
Gnomad EAS
AF:
0.0239
Gnomad SAS
AF:
0.169
Gnomad FIN
AF:
0.0530
Gnomad MID
AF:
0.0601
Gnomad NFE
AF:
0.0560
Gnomad OTH
AF:
0.0684
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0552
AC:
8406
AN:
152246
Hom.:
302
Cov.:
32
AF XY:
0.0571
AC XY:
4252
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0456
Gnomad4 AMR
AF:
0.0494
Gnomad4 ASJ
AF:
0.0681
Gnomad4 EAS
AF:
0.0237
Gnomad4 SAS
AF:
0.168
Gnomad4 FIN
AF:
0.0530
Gnomad4 NFE
AF:
0.0560
Gnomad4 OTH
AF:
0.0676
Alfa
AF:
0.0148
Hom.:
5
Bravo
AF:
0.0520
Asia WGS
AF:
0.114
AC:
397
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
4.1
DANN
Benign
0.46

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.

Other links and lift over

dbSNP: rs17186372; hg19: chr1-120500951; API