rs114926520

Variant names:

• chr2-15941822-G-A
• rs114926520
• NM_005378.6:c.-117-126G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005378.6(MYCN):​c.-117-126G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 595,640 control chromosomes in the GnomAD database, including 203 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (39 hom., cov: 33)
  • Exomes 𝑓: 0.018 (164 hom.)
• Consequence: MYCN NM_005378.6 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0680
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-15941822-G-A is Benign according to our data. Variant chr2-15941822-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1191232.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0542 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005378.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCN	NM_005378.6	MANE Select	c.-117-126G>A		intron	N/A	NP_005369.2
	MYCN	NM_001293228.2		c.-117-126G>A		intron	N/A	NP_001280157.1	P04198
	MYCN	NM_001293231.2		c.157+1079G>A		intron	N/A	NP_001280160.1	A0A1W2PPD9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYCN	ENST00000281043.4	TSL:5 MANE Select	c.-117-126G>A		intron	N/A	ENSP00000281043.3	P04198
	MYCN	ENST00000930196.1		c.-243G>A		5_prime_UTR	Exon 1 of 2	ENSP00000600255.1
	MYCN	ENST00000885101.1		c.-117-126G>A		intron	N/A	ENSP00000555160.1

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2589 AN: 152164 Hom.: 38 Cov.: 33

Gnomad AFR AF: 0.0184

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0127

Gnomad ASJ AF: 0.0109

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0602

Gnomad FIN AF: 0.00810

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0139

GnomAD4 exome AF: 0.0182 AC: 8075 AN: 443360 Hom.: 164 Cov.: 3 AF XY: 0.0205 AC XY: 4789 AN XY: 233290

African (AFR) AF: 0.0194 AC: 238 AN: 12290

American (AMR) AF: 0.0103 AC: 191 AN: 18474

Ashkenazi Jewish (ASJ) AF: 0.0104 AC: 141 AN: 13596

East Asian (EAS) AF: 0.000163 AC: 5 AN: 30654

South Asian (SAS) AF: 0.0554 AC: 2517 AN: 45438

European-Finnish (FIN) AF: 0.00844 AC: 245 AN: 29028

Middle Eastern (MID) AF: 0.0406 AC: 79 AN: 1944

European-Non Finnish (NFE) AF: 0.0160 AC: 4253 AN: 266188

Other (OTH) AF: 0.0158 AC: 406 AN: 25748

GnomAD4 genome AF: 0.0170 AC: 2596 AN: 152280 Hom.: 39 Cov.: 33 AF XY: 0.0176 AC XY: 1314 AN XY: 74452

African (AFR) AF: 0.0185 AC: 769 AN: 41564

American (AMR) AF: 0.0127 AC: 194 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 38 AN: 3472

East Asian (EAS) AF: 0.00233 AC: 12 AN: 5160

South Asian (SAS) AF: 0.0599 AC: 289 AN: 4826

European-Finnish (FIN) AF: 0.00810 AC: 86 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1137 AN: 68018

Other (OTH) AF: 0.0151 AC: 32 AN: 2114

Alfa AF: 0.0175 Hom.: 6

Bravo AF: 0.0151

Asia WGS AF: 0.0270 AC: 92 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	8.6
DANN	Benign	0.86
PhyloP100		-0.068
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114926520; hg19: chr2-16081944;