Genetic Variant NM_022828.5:c.3355-261G>A (chr5-113581156-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Publications

3 publications found

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:

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ACMG classification

Classification was made for transcript

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YTHDC2	ENST00000161863.9	TSL:1 MANE Select	c.3355-261G>A	intron	N/A	ENSP00000161863.4	Q9H6S0
YTHDC2	ENST00000935143.1		c.3448-261G>A	intron	N/A	ENSP00000605202.1
YTHDC2	ENST00000873029.1		c.3355-261G>A	intron	N/A	ENSP00000543088.1

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29228

AN:

151920

Hom.:

2925

Cov.:

show subpopulations

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

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1130

2260

3391

4521

5651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.192

AC:

29234

AN:

152038

Hom.:

2927

Cov.:

AF XY:

0.187

AC XY:

13924

AN XY:

74312

show subpopulations

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:

AN:

292

European-Non Finnish (NFE)

AF:

0.231

AC:

15672

AN:

67982

Other (OTH)

AF:

0.181

AC:

382

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1211

2423

3634

4846

6057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.44

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over