5-113581156-G-A

Position:

• chr5-113581156-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022828.5(YTHDC2):​c.3355-261G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 301,538 control chromosomes in the GnomAD database, including 5,997 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2927 hom., cov: 32)
  • Exomes 𝑓: 0.19 (3070 hom.)
• Consequence: YTHDC2 NM_022828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00

Genes affected

YTHDC2 (HGNC:24721): (YTH N6-methyladenosine RNA binding protein C2) This gene encodes a member of the DEAH (Asp-Glu-Ala-His) subfamily of proteins, part of the DEAD (Asp-Glu-Ala-Asp) box family of RNA helicases. The encoded protein binds to N6-methyladenosine, a common modified RNA nucleotide that is enriched in the stop codons and 3' UTRs of eukaryotic messenger RNAs. Binding of proteins to this modified nucleotide may regulate mRNA translation and stability. This gene may be associated with susceptibility to pancreatic cancer in human patients, and knockdown of this gene resulted in reduced proliferation in a human liver cancer cell line. [provided by RefSeq, Sep 2016]

YTHDC2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YTHDC2	NM_022828.5	c.3355-261G>A		intron_variant		ENST00000161863.9	NP_073739.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YTHDC2	ENST00000161863.9	c.3355-261G>A		intron_variant		1	NM_022828.5	ENSP00000161863.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29228 AN: 151920 Hom.: 2925 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.171

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.231

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.192 AC: 28693 AN: 149500 Hom.: 3070 AF XY: 0.191 AC XY: 14694 AN XY: 76920

Gnomad4 AFR exome AF: 0.153

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.0641

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.189

GnomAD4 genome AF: 0.192 AC: 29234 AN: 152038 Hom.: 2927 Cov.: 32 AF XY: 0.187 AC XY: 13924 AN XY: 74312

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.171

Gnomad4 NFE AF: 0.231

Gnomad4 OTH AF: 0.181

Alfa AF: 0.201 Hom.: 510

Bravo AF: 0.188

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.44

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: rs6883547; hg19: chr5-112916853;