Variant 5-113515266-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_022828.5(YTHDC2):c.188-6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 1,592,016 control chromosomes in the GnomAD database, including 10,173 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.11 ( 1119 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9054 hom. )

Consequence

YTHDC2
NM_022828.5 splice_region, intron

Scores

Splicing: ADA: 0.00009098

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -1.07

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 5-113515266-G-A is Benign according to our data. Variant chr5-113515266-G-A is described in ClinVar as [Benign]. Clinvar id is 3037545.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YTHDC2	NM_022828.5 linkuse as main transcript	c.188-6G>A		splice_region_variant, intron_variant		ENST00000161863.9	NP_073739.3	Q9H6S0

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
YTHDC2	ENST00000161863.9 linkuse as main transcript	c.188-6G>A	splice_region_variant, intron_variant	1	NM_022828.5	ENSP00000161863.4	Q9H6S0
YTHDC2	ENST00000515883.5 linkuse as main transcript	c.188-6G>A	splice_region_variant, intron_variant	1		ENSP00000423101.1	D6RA70
YTHDC2	ENST00000514720.1 linkuse as main transcript	c.8-6G>A	splice_region_variant, intron_variant	4		ENSP00000422916.1	D6R9T8
YTHDC2	ENST00000503857.5 linkuse as main transcript	n.188-6G>A	splice_region_variant, intron_variant	5		ENSP00000426644.1	D6RF50

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17391

AN:

151494

Hom.:

1115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.139

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.0648

Gnomad ASJ

AF:

0.102

Gnomad EAS

AF:

0.0279

Gnomad SAS

AF:

0.0754

Gnomad FIN

AF:

0.201

Gnomad MID

AF:

0.0737

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.0904

GnomAD3 exomes

AF:

0.0975

AC:

23331

AN:

239402

Hom.:

1453

AF XY:

0.0979

AC XY:

12662

AN XY:

129372

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.0402

Gnomad ASJ exome

AF:

0.0938

Gnomad EAS exome

AF:

0.0191

Gnomad SAS exome

AF:

0.0790

Gnomad FIN exome

AF:

0.201

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0877

GnomAD4 exome

AF:

0.108

AC:

155892

AN:

1440406

Hom.:

9054

Cov.:

AF XY:

0.107

AC XY:

76884

AN XY:

715812

show subpopulations

Gnomad4 AFR exome

AF:

0.144

Gnomad4 AMR exome

AF:

0.0431

Gnomad4 ASJ exome

AF:

0.0946

Gnomad4 EAS exome

AF:

0.0304

Gnomad4 SAS exome

AF:

0.0799

Gnomad4 FIN exome

AF:

0.194

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.101

GnomAD4 genome

AF:

0.115

AC:

17424

AN:

151610

Hom.:

1119

Cov.:

AF XY:

0.117

AC XY:

8645

AN XY:

74070

show subpopulations

Gnomad4 AFR

AF:

0.139

Gnomad4 AMR

AF:

0.0647

Gnomad4 ASJ

AF:

0.102

Gnomad4 EAS

AF:

0.0279

Gnomad4 SAS

AF:

0.0749

Gnomad4 FIN

AF:

0.201

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.0981

Hom.:

519

Bravo

AF:

0.105

Asia WGS

AF:

0.106

AC:

370

AN:

3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

YTHDC2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 30, 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). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.44

DANN

Benign

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.0

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