Genetic Variant DDC:c.435+260G>A (chr7-50537600-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001082971.2(DDC):c.435+260G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 152,154 control chromosomes in the GnomAD database, including 3,797 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 3797 hom., cov: 32)

Consequence

DDC
NM_001082971.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.766

Publications

9 publications found

Variant links:

Genes affected

DDC (HGNC:2719): (dopa decarboxylase) The encoded protein catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in this gene are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2011]

DDC links:

DDC-AS1 (HGNC:40171): (DDC antisense RNA 1)

DDC-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 7-50537600-C-T is Benign according to our data. Variant chr7-50537600-C-T is described in ClinVar as Benign. ClinVar VariationId is 1251771.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDC	NM_001082971.2	MANE Select	c.435+260G>A	intron	N/A	NP_001076440.2	A0A0S2Z3N4
DDC	NM_000790.4		c.435+260G>A	intron	N/A	NP_000781.2	P20711-1
DDC	NM_001242886.2		c.321+260G>A	intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DDC	ENST00000444124.7	TSL:1 MANE Select	c.435+260G>A	intron	N/A	ENSP00000403644.2	P20711-1
DDC	ENST00000357936.9	TSL:1	c.435+260G>A	intron	N/A	ENSP00000350616.5	P20711-1
DDC	ENST00000380984.4	TSL:1	c.435+260G>A	intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes

AF:

0.219

AC:

33352

AN:

152036

Hom.:

3797

Cov.:

show subpopulations

Gnomad AFR

AF:

0.216

Gnomad AMI

AF:

0.270

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.196

Gnomad EAS

AF:

0.395

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.218

Gnomad OTH

AF:

0.211

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.219

AC:

33345

AN:

152154

Hom.:

3797

Cov.:

AF XY:

0.219

AC XY:

16289

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.215

AC:

8930

AN:

41498

American (AMR)

AF:

0.162

AC:

2472

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.196

AC:

680

AN:

3470

East Asian (EAS)

AF:

0.394

AC:

2037

AN:

5172

South Asian (SAS)

AF:

0.309

AC:

1490

AN:

4824

European-Finnish (FIN)

AF:

0.200

AC:

2122

AN:

10592

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.218

AC:

14830

AN:

67988

Other (OTH)

AF:

0.215

AC:

454

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1333

2666

3999

5332

6665

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

364

728

1092

1456

1820

<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:

0.215

Hom.:

643

Bravo

AF:

0.216

Asia WGS

AF:

0.320

AC:

1112

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.2

(source)

DANN

Benign

0.77

PhyloP100

-0.77

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over