5-113581156-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_022828.5(YTHDC2):​c.3355-261G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000667 in 149,958 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000067 (0 hom.)
• Consequence: YTHDC2 NM_022828.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 0 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: 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=-0.91).

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>T		intron	N/A	NP_073739.3
	YTHDC2	NM_001345975.2		c.2869-261G>T		intron	N/A	NP_001332904.1
	YTHDC2	NM_001345976.2		c.2455-261G>T		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>T		intron	N/A	ENSP00000161863.4
	YTHDC2	ENST00000512600.1	TSL:2	n.-110G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000667 AC: 1 AN: 149958 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 77134

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4440

American (AMR) AF: 0.00 AC: 0 AN: 5348

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5612

East Asian (EAS) AF: 0.00 AC: 0 AN: 11098

South Asian (SAS) AF: 0.00 AC: 0 AN: 5640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8080

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 790

European-Non Finnish (NFE) AF: 0.0000101 AC: 1 AN: 99020

Other (OTH) AF: 0.00 AC: 0 AN: 9930

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.50
PhyloP100		-1.0

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;