Variant 2-15940647-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001293231.2(MYCN):c.61G>T(p.Ala21Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 400,356 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 0 hom. )

Consequence

MYCN
NM_001293231.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.40

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]

MYCN links:

MYCNOS (HGNC:16911): (MYCN opposite strand) This gene is transcribed in antisense to the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog gene (MYCN). It is thought to encode a small, novel protein that stabilizes MYCN, prevents apoptosis, and promotes cell proliferation. Transcripts at this locus may also act directly as functional RNAs to recruit transcriptional regulators to the promoter of MYCN and stimulate transcription of this oncogene. This gene therefore functions through both RNA and protein products. [provided by RefSeq, Aug 2016]

MYCNOS links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.032213688).

BP6

Variant 2-15940647-G-T is Benign according to our data. Variant chr2-15940647-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2650691.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-15940647-G-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00147 (224/152250) while in subpopulation NFE AF= 0.00246 (167/68000). AF 95% confidence interval is 0.00215. There are 0 homozygotes in gnomad4. There are 97 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 224 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCN	NM_005378.6 link	c.-214G>T		5_prime_UTR_variant	1/3	ENST00000281043.4	NP_005369.2	P04198

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYCN	ENST00000281043 link	c.-214G>T		5_prime_UTR_variant	1/3	5	NM_005378.6	ENSP00000281043.3		P04198

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

224

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000773

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.00192

GnomAD4 exome

AF:

0.00172

AC:

426

AN:

248106

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

232

AN XY:

125670

show subpopulations

Gnomad4 AFR exome

AF:

0.000276

Gnomad4 AMR exome

AF:

0.00134

Gnomad4 ASJ exome

AF:

0.000974

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00161

Gnomad4 FIN exome

AF:

0.000432

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.00147

AC:

224

AN:

152250

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000775

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.00150

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00234

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MYCN-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 22, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2024

MYCN: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.95

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.44

MetaRNN

Benign

0.032

GERP RS

2.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over