rs1553370205

Variant names:

• chr2-15941939-C-T
• rs1553370205
• NM_005378.6:c.-117-9C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_005378.6(MYCN):​c.-117-9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYCN NM_005378.6 intron
• Scores: Splicing: ADA: 0.0004531
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.247
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 2-15941939-C-T is Benign according to our data. Variant chr2-15941939-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 510953.Status of the report is criteria_provided_single_submitter, 1 stars.

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.-117-9C>T		intron	N/A	NP_005369.2
	MYCN	NM_001293228.2		c.-117-9C>T		intron	N/A	NP_001280157.1	P04198
	MYCN	NM_001293231.2		c.157+1196C>T		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.-117-9C>T		intron	N/A	ENSP00000281043.3	P04198
	MYCN	ENST00000930196.1		c.-126C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 2	ENSP00000600255.1
	MYCN	ENST00000930196.1		c.-126C>T		5_prime_UTR	Exon 1 of 2	ENSP00000600255.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1044502 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 525458

African (AFR) AF: 0.00 AC: 0 AN: 24932

American (AMR) AF: 0.00 AC: 0 AN: 33688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20620

East Asian (EAS) AF: 0.00 AC: 0 AN: 34096

South Asian (SAS) AF: 0.00 AC: 0 AN: 66358

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4400

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 771592

Other (OTH) AF: 0.00 AC: 0 AN: 46342

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	17
DANN	Benign	0.97
PhyloP100		-0.25
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00045
dbscSNV1_RF	Benign	0.066
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: rs1553370205; hg19: chr2-16082061;