rs6883547

Variant names:

• chr5-113581156-G-A
• rs6883547
• NM_022828.5:c.3355-261G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-113581156-G-A
• chr5-113581156-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022828.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDC2	NM_022828.5	MANE Select	c.3355-261G>A		intron	N/A	NP_073739.3
	YTHDC2	NM_001345975.2		c.2869-261G>A		intron	N/A	NP_001332904.1
	YTHDC2	NM_001345976.2		c.2455-261G>A		intron	N/A	NP_001332905.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YTHDC2	ENST00000161863.9	TSL:1 MANE Select	c.3355-261G>A		intron	N/A	ENSP00000161863.4
	YTHDC2	ENST00000512600.1	TSL:2	n.-110G>A		upstream_gene	N/A

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

African (AFR) AF: 0.153 AC: 678 AN: 4430

American (AMR) AF: 0.119 AC: 635 AN: 5330

Ashkenazi Jewish (ASJ) AF: 0.143 AC: 800 AN: 5582

East Asian (EAS) AF: 0.0641 AC: 711 AN: 11084

South Asian (SAS) AF: 0.123 AC: 690 AN: 5626

European-Finnish (FIN) AF: 0.179 AC: 1439 AN: 8046

Middle Eastern (MID) AF: 0.154 AC: 121 AN: 784

European-Non Finnish (NFE) AF: 0.220 AC: 21746 AN: 98708

Other (OTH) AF: 0.189 AC: 1873 AN: 9910

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

African (AFR) AF: 0.172 AC: 7145 AN: 41484

American (AMR) AF: 0.147 AC: 2244 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3468

East Asian (EAS) AF: 0.0893 AC: 463 AN: 5182

South Asian (SAS) AF: 0.139 AC: 668 AN: 4812

European-Finnish (FIN) AF: 0.171 AC: 1805 AN: 10534

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.231 AC: 15672 AN: 67982

Other (OTH) AF: 0.181 AC: 382 AN: 2112

Alfa AF: 0.201 Hom.: 518

Bravo AF: 0.188

Asia WGS AF: 0.0980 AC: 342 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.13
DANN	Benign	0.44
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs6883547; hg19: chr5-112916853;