Genetic Variant DCTD:c.108+124G>A (chr4-182915337-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001012732.2(DCTD):c.141+124G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 766,396 control chromosomes in the GnomAD database, including 15,728 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 0.17 ( 2359 hom., cov: 33)

Exomes 𝑓: 0.20 ( 13369 hom. )

Consequence

DCTD
NM_001012732.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.826

Publications

7 publications found

Variant links:

Genes affected

DCTD (HGNC:2710): (dCMP deaminase) The protein encoded by this gene catalyzes the deamination of dCMP to dUMP, the nucleotide substrate for thymidylate synthase. The encoded protein is allosterically activated by dCTP and inhibited by dTTP, and is found as a homohexamer. This protein uses zinc as a cofactor for its activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DCTD links:

Genome browser will be placed here

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=-0.8).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012732.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DCTD	NM_001921.3	MANE Select	c.108+124G>A	intron	N/A	NP_001912.2
DCTD	NM_001012732.2		c.141+124G>A	intron	N/A	NP_001012750.1
DCTD	NM_001351743.2		c.108+124G>A	intron	N/A	NP_001338672.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DCTD	ENST00000438320.7	TSL:1 MANE Select	c.108+124G>A	intron	N/A	ENSP00000398194.2
DCTD	ENST00000357067.7	TSL:1	c.141+124G>A	intron	N/A	ENSP00000349576.3
DCTD	ENST00000507631.5	TSL:1	n.108+124G>A	intron	N/A	ENSP00000425287.1

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25489

AN:

152094

Hom.:

2360

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0832

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.175

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.205

AC:

125807

AN:

614184

Hom.:

13369

AF XY:

0.204

AC XY:

66597

AN XY:

325970

show subpopulations

African (AFR)

AF:

0.0860

AC:

1426

AN:

16574

American (AMR)

AF:

0.138

AC:

4032

AN:

29156

Ashkenazi Jewish (ASJ)

AF:

0.153

AC:

2537

AN:

16528

East Asian (EAS)

AF:

0.232

AC:

8234

AN:

35452

South Asian (SAS)

AF:

0.174

AC:

9833

AN:

56470

European-Finnish (FIN)

AF:

0.199

AC:

8407

AN:

42172

Middle Eastern (MID)

AF:

0.155

AC:

611

AN:

3954

European-Non Finnish (NFE)

AF:

0.221

AC:

84452

AN:

381778

Other (OTH)

AF:

0.195

AC:

6275

AN:

32100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

5173

10345

15518

20690

25863

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1184

2368

3552

4736

5920

<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:

0.167

AC:

25484

AN:

152212

Hom.:

2359

Cov.:

AF XY:

0.167

AC XY:

12407

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0830

AC:

3450

AN:

41556

American (AMR)

AF:

0.136

AC:

2085

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

490

AN:

3470

East Asian (EAS)

AF:

0.261

AC:

1344

AN:

5156

South Asian (SAS)

AF:

0.175

AC:

845

AN:

4826

European-Finnish (FIN)

AF:

0.182

AC:

1934

AN:

10602

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14795

AN:

67994

Other (OTH)

AF:

0.156

AC:

331

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1090

2180

3269

4359

5449

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<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:

0.199

Hom.:

3250

Bravo

AF:

0.162

Asia WGS

AF:

0.220

AC:

764

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.27

(source)

DANN

Benign

0.79

PhyloP100

-0.83

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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