dbSNP rs3829897: DDC:c.-29+3218C>A (chr7-50562067-G-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_001082971.2(DDC):c.-29+3218C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,016 control chromosomes in the GnomAD database, including 17,329 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 0.47 ( 17329 hom., cov: 33)

Consequence

DDC
NM_001082971.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.24

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 Gene-Disease associations (from GenCC):

aromatic L-amino acid decarboxylase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

DDC 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=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2 link	c.-29+3218C>A	intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2	P20711-1Q53Y41A0A0S2Z3N4
DDC	XM_047419932.1 link	c.-29+3218C>A	intron_variant	Intron 1 of 15		XP_047275888.1
DDC	XM_047419931.1 link	c.-29+3218C>A	intron_variant	Intron 1 of 13		XP_047275887.1
DDC	XM_005271745.5 link	c.-29+3218C>A	intron_variant	Intron 1 of 13		XP_005271802.1	A0A087WV24

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7 link	c.-29+3218C>A		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2		P20711-1
DDC	ENST00000420203.1 link	c.-29+1928C>A		intron_variant	Intron 1 of 1	2		ENSP00000408626.1		C9JMP0

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70963

AN:

151898

Hom.:

17301

Cov.:

show subpopulations

Gnomad AFR

AF:

0.586

Gnomad AMI

AF:

0.340

Gnomad AMR

AF:

0.423

Gnomad ASJ

AF:

0.323

Gnomad EAS

AF:

0.623

Gnomad SAS

AF:

0.504

Gnomad FIN

AF:

0.547

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.420

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

GnomAD4 genome

AF:

0.467

AC:

71042

AN:

152016

Hom.:

17329

Cov.:

AF XY:

0.477

AC XY:

35408

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.586

AC:

24279

AN:

41436

American (AMR)

AF:

0.423

AC:

6463

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

1120

AN:

3470

East Asian (EAS)

AF:

0.622

AC:

3215

AN:

5168

South Asian (SAS)

AF:

0.505

AC:

2431

AN:

4812

European-Finnish (FIN)

AF:

0.547

AC:

5777

AN:

10568

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26446

AN:

67970

Other (OTH)

AF:

0.422

AC:

891

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1913

3826

5739

7652

9565

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

640

1280

1920

2560

3200

<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:

0.412

Hom.:

8200

Bravo

AF:

0.465

Asia WGS

AF:

0.515

AC:

1790

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.27

(source)

DANN

Benign

0.39

PhyloP100

-1.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over