dbSNP rs3837091: DDC:c.-61_-58delAGAG (chr7-50561042-CCTCT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000357936.9(DDC):c.-61_-58delAGAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,836 control chromosomes in the GnomAD database, including 4,587 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4586 hom., cov: 24)

Exomes 𝑓: 0.20 ( 1 hom. )

Consequence

DDC
ENST00000357936.9 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.812

Publications

17 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 -10 ACMG points.

BP6

Variant 7-50561042-CCTCT-C is Benign according to our data. Variant chr7-50561042-CCTCT-C is described in ClinVar as [Benign]. Clinvar id is 360446.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2 link	c.-29+4239_-29+4242delAGAG		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2	P20711-1Q53Y41A0A0S2Z3N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7 link	c.-29+4239_-29+4242delAGAG		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2		P20711-1

Frequencies

GnomAD3 genomes

AF:

0.240

AC:

36363

AN:

151660

Hom.:

4582

Cov.:

show subpopulations

Gnomad AFR

AF:

0.186

Gnomad AMI

AF:

0.277

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.505

Gnomad SAS

AF:

0.314

Gnomad FIN

AF:

0.283

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.245

Gnomad OTH

AF:

0.229

GnomAD4 exome

AF:

0.200

AC:

AN:

Hom.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.225

AC:

AN:

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.240

AC:

36365

AN:

151776

Hom.:

4586

Cov.:

AF XY:

0.243

AC XY:

18027

AN XY:

74146

show subpopulations

African (AFR)

AF:

0.186

AC:

7698

AN:

41410

American (AMR)

AF:

0.220

AC:

3356

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

782

AN:

3466

East Asian (EAS)

AF:

0.504

AC:

2569

AN:

5098

South Asian (SAS)

AF:

0.316

AC:

1520

AN:

4806

European-Finnish (FIN)

AF:

0.283

AC:

2975

AN:

10522

Middle Eastern (MID)

AF:

0.248

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.245

AC:

16653

AN:

67912

Other (OTH)

AF:

0.232

AC:

488

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1391

2783

4174

5566

6957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0974

Hom.:

165

Bravo

AF:

0.236

Asia WGS

AF:

0.367

AC:

1277

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of aromatic-L-amino-acid decarboxylase

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.81

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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rs3837091

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over