dbSNP rs1466163: DDC:c.315+407T>C (chr7-50539508-A-G) – 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.315+407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,236 control chromosomes in the GnomAD database, including 62,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.90 ( 62302 hom., cov: 31)

Consequence

DDC
NM_001082971.2 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0460

Publications

6 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:

Genome browser will be placed here

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=-0.99).

BP6

Variant 7-50539508-A-G is Benign according to our data. Variant chr7-50539508-A-G is described in ClinVar as Benign. ClinVar VariationId is 3256803.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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.315+407T>C	intron	N/A	NP_001076440.2	A0A0S2Z3N4
DDC	NM_000790.4		c.315+407T>C	intron	N/A	NP_000781.2	P20711-1
DDC	NM_001242886.2		c.202-1529T>C	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.315+407T>C	intron	N/A	ENSP00000403644.2	P20711-1
DDC	ENST00000357936.9	TSL:1	c.315+407T>C	intron	N/A	ENSP00000350616.5	P20711-1
DDC	ENST00000380984.4	TSL:1	c.315+407T>C	intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes

AF:

0.904

AC:

137545

AN:

152118

Hom.:

62256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.917

Gnomad AMI

AF:

0.968

Gnomad AMR

AF:

0.914

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.997

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.922

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.884

Gnomad OTH

AF:

0.900

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

GnomAD4 genome

AF:

0.904

AC:

137652

AN:

152236

Hom.:

62302

Cov.:

AF XY:

0.906

AC XY:

67429

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.917

AC:

38094

AN:

41534

American (AMR)

AF:

0.914

AC:

13987

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.916

AC:

3180

AN:

3470

East Asian (EAS)

AF:

0.997

AC:

5151

AN:

5166

South Asian (SAS)

AF:

0.885

AC:

4260

AN:

4814

European-Finnish (FIN)

AF:

0.922

AC:

9782

AN:

10608

Middle Eastern (MID)

AF:

0.888

AC:

261

AN:

294

European-Non Finnish (NFE)

AF:

0.884

AC:

60148

AN:

68020

Other (OTH)

AF:

0.902

AC:

1906

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

677

1354

2032

2709

3386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

906

1812

2718

3624

4530

<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:

0.890

Hom.:

12078

Bravo

AF:

0.906

Asia WGS

AF:

0.936

AC:

3257

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

6.3

(source)

DANN

Benign

0.35

PhyloP100

-0.046

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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