chr2-15940678-G-C

Variant names:

• chr2-15940678-G-C
• rs1241796486
• ENST00000281043:c.-183G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001293231.2(MYCN):​c.92G>C​(p.Arg31Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R31H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.074 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYCN NM_001293231.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.15255892).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYCN	NM_005378.6	c.-183G>C		5_prime_UTR_variant	Exon 1 of 3	ENST00000281043.4	NP_005369.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYCN	ENST00000281043	c.-183G>C		5_prime_UTR_variant	Exon 1 of 3	5	NM_005378.6	ENSP00000281043.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 560 AN: 145068 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00293

Gnomad AMI AF: 0.00568

Gnomad AMR AF: 0.00395

Gnomad ASJ AF: 0.000596

Gnomad EAS AF: 0.0226

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.00799

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.000492

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0740 AC: 4803 AN: 64912 Hom.: 0 Cov.: 0 AF XY: 0.0753 AC XY: 2476 AN XY: 32886

Gnomad4 AFR exome AF: 0.0759

Gnomad4 AMR exome AF: 0.0812

Gnomad4 ASJ exome AF: 0.0728

Gnomad4 EAS exome AF: 0.0564

Gnomad4 SAS exome AF: 0.0630

Gnomad4 FIN exome AF: 0.0991

Gnomad4 NFE exome AF: 0.0751

Gnomad4 OTH exome AF: 0.0760

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00380 AC: 552 AN: 145204 Hom.: 0 Cov.: 32 AF XY: 0.00383 AC XY: 271 AN XY: 70690

Gnomad4 AFR AF: 0.00287

Gnomad4 AMR AF: 0.00394

Gnomad4 ASJ AF: 0.000596

Gnomad4 EAS AF: 0.0224

Gnomad4 SAS AF: 0.0204

Gnomad4 FIN AF: 0.00799

Gnomad4 NFE AF: 0.00168

Gnomad4 OTH AF: 0.000487

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.87
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.15	T
GERP RS		1.2

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

Other links and lift over

dbSNP: rs1241796486; hg19: chr2-16080800;