rs1553370260

Variant summary

Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate

The NM_005378.6(MYCN):​c.68_71dupCGCT​(p.Gln25fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 33)

Consequence

MYCN
NM_005378.6 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 2.63
Variant links:
Genes affected
MYCN (HGNC:7559): (MYCN proto-oncogene, bHLH transcription factor) This gene is a member of the MYC family and encodes a protein with a basic helix-loop-helix (bHLH) domain. This protein is located in the nucleus and must dimerize with another bHLH protein in order to bind DNA. Amplification of this gene is associated with a variety of tumors, most notably neuroblastomas. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 8 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. There are 9 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-15942129-A-ACTCG is Pathogenic according to our data. Variant chr2-15942129-A-ACTCG is described in ClinVar as [Pathogenic]. Clinvar id is 433150.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYCNNM_005378.6 linkuse as main transcriptc.68_71dupCGCT p.Gln25fs frameshift_variant 2/3 ENST00000281043.4 NP_005369.2 P04198

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYCNENST00000281043.4 linkuse as main transcriptc.68_71dupCGCT p.Gln25fs frameshift_variant 2/35 NM_005378.6 ENSP00000281043.3 P04198
MYCNENST00000638417.1 linkuse as main transcriptc.157+1389_157+1392dupCGCT intron_variant 2 ENSP00000491476.1 A0A1W2PPD9
MYCNOSENST00000641534.1 linkuse as main transcriptn.98+19_98+22dupCGAG intron_variant

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Feingold syndrome type 1 Pathogenic:1
Pathogenic, criteria provided, single submitterclinical testingMolecular Diagnostics Lab, Nemours Children's Health, DelawareJan 12, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs1553370260; hg19: chr2-16082251; API