Variant 2-15940691-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_001293231.2(MYCN):c.105A>C(p.Pro35Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYCN
NM_001293231.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.495

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-15940691-A-C is Benign according to our data. Variant chr2-15940691-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2650692.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-15940691-A-C is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=0.495 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYCN	NM_005378.6 link	c.-170A>C		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.-170A>C		5_prime_UTR_variant	1/3	5	NM_005378.6	ENSP00000281043.3		P04198

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

140964

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000490

Gnomad AMI

AF:

0.00117

Gnomad AMR

AF:

0.000626

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00402

Gnomad SAS

AF:

0.00489

Gnomad FIN

AF:

0.00206

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000233

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00668

AC:

449

AN:

67262

Hom.:

Cov.:

AF XY:

0.00644

AC XY:

218

AN XY:

33856

show subpopulations

Gnomad4 AFR exome

AF:

0.00945

Gnomad4 AMR exome

AF:

0.00800

Gnomad4 ASJ exome

AF:

0.00818

Gnomad4 EAS exome

AF:

0.00631

Gnomad4 SAS exome

AF:

0.00313

Gnomad4 FIN exome

AF:

0.00503

Gnomad4 NFE exome

AF:

0.00681

Gnomad4 OTH exome

AF:

0.00751

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000695

AC:

AN:

141066

Hom.:

Cov.:

AF XY:

0.000672

AC XY:

AN XY:

68416

show subpopulations

Gnomad4 AFR

AF:

0.000488

Gnomad4 AMR

AF:

0.000625

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00403

Gnomad4 SAS

AF:

0.00464

Gnomad4 FIN

AF:

0.00206

Gnomad4 NFE

AF:

0.000233

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

MYCN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.91

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