5-113513930-C-T

Position:

chr5-113513930-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001345975.2(YTHDC2):c.-255C>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 0.00117 in 1,605,508 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00062 ( 11 hom. )

Consequence

YTHDC2
NM_001345975.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0046419203).

BP6

Variant 5-113513930-C-T is Benign according to our data. Variant chr5-113513930-C-T is described in ClinVar as [Benign]. Clinvar id is 776057.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00648 (987/152340) while in subpopulation AFR AF= 0.0221 (920/41582). AF 95% confidence interval is 0.0209. There are 7 homozygotes in gnomad4. There are 468 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 987 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YTHDC2	NM_022828.5 linkuse as main transcript	c.35C>T	p.Pro12Leu	missense_variant	1/30	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.35C>T	p.Pro12Leu	missense_variant	1/30	1	NM_022828.5	ENSP00000161863.4	Q9H6S0
YTHDC2	ENST00000515883.5 linkuse as main transcript	c.35C>T	p.Pro12Leu	missense_variant	1/17	1		ENSP00000423101.1	D6RA70
YTHDC2	ENST00000503857.5 linkuse as main transcript	n.35C>T		non_coding_transcript_exon_variant	1/16	5		ENSP00000426644.1	D6RF50

Frequencies

GnomAD3 genomes

AF:

0.00648

AC:

987

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00149

AC:

341

AN:

228386

Hom.:

AF XY:

0.00113

AC XY:

142

AN XY:

125912

show subpopulations

Gnomad AFR exome

AF:

0.0247

Gnomad AMR exome

AF:

0.000774

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000340

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000599

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.000617

AC:

896

AN:

1453168

Hom.:

Cov.:

AF XY:

0.000530

AC XY:

383

AN XY:

722076

show subpopulations

Gnomad4 AFR exome

AF:

0.0226

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00119

GnomAD4 genome

AF:

0.00648

AC:

987

AN:

152340

Hom.:

Cov.:

AF XY:

0.00628

AC XY:

468

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0221

Gnomad4 AMR

AF:

0.00340

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.000277

Hom.:

Bravo

AF:

0.00768

ESP6500AA

AF:

0.0181

AC:

ESP6500EA

AF:

0.000128

AC:

ExAC

AF:

0.00189

AC:

225

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

YTHDC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 24, 2019

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

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0028

T;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.80

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-0.78

N;N

REVEL

Benign

0.070

Sift

Benign

0.059

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.16

B;.

Vest4

0.17

MVP

0.043

MPC

0.095

ClinPred

0.031

GERP RS

3.6

Varity_R

0.039

gMVP

0.47

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