Variant 5-113532986-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001345976.2(YTHDC2):c.-118C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000445 in 1,614,072 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

YTHDC2
NM_001345976.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.05

Variant links:

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 links:

YTHDC2 (HGNC:):

YTHDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.26).

BP6

Variant 5-113532986-C-T is Benign according to our data. Variant chr5-113532986-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3057587.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YTHDC2	NM_022828.5 linkuse as main transcript	c.783C>T	p.Ala261Ala	synonymous_variant	5/30	ENST00000161863.9	NP_073739.3	Q9H6S0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
YTHDC2	ENST00000161863.9 linkuse as main transcript	c.783C>T	p.Ala261Ala	synonymous_variant	5/30	1	NM_022828.5	ENSP00000161863.4	Q9H6S0
YTHDC2	ENST00000515883.5 linkuse as main transcript	c.783C>T	p.Ala261Ala	synonymous_variant	5/17	1		ENSP00000423101.1	D6RA70
YTHDC2	ENST00000503857.5 linkuse as main transcript	n.*89C>T		non_coding_transcript_exon_variant	3/16	5		ENSP00000426644.1	D6RF50
YTHDC2	ENST00000503857.5 linkuse as main transcript	n.*89C>T		3_prime_UTR_variant	3/16	5		ENSP00000426644.1	D6RF50

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000573

AC:

144

AN:

251414

Hom.:

AF XY:

0.000581

AC XY:

AN XY:

135870

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000985

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000451

AC:

660

AN:

1461856

Hom.:

Cov.:

AF XY:

0.000487

AC XY:

354

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000313

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.000488

Gnomad4 OTH exome

AF:

0.000679

GnomAD4 genome

AF:

0.000388

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000785

Hom.:

Bravo

AF:

0.000487

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00142

EpiControl

AF:

0.00178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

YTHDC2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.77

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over