rs1817074

Variant names:

• chr7-50506314-T-C
• rs1817074
• NM_001082971.2:c.715-2255A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):​c.715-2255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.371 in 151,900 control chromosomes in the GnomAD database, including 10,715 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 0.37 (10715 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 11 publications found

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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.435 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.715-2255A>G		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.715-2255A>G		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.601-2255A>G		intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.715-2255A>G		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.715-2255A>G		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.715-2255A>G		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56269 AN: 151782 Hom.: 10693 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.358

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

GnomAD4 genome AF: 0.371 AC: 56335 AN: 151900 Hom.: 10715 Cov.: 31 AF XY: 0.378 AC XY: 28051 AN XY: 74244

African (AFR) AF: 0.399 AC: 16513 AN: 41406

American (AMR) AF: 0.444 AC: 6786 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1018 AN: 3468

East Asian (EAS) AF: 0.199 AC: 1030 AN: 5164

South Asian (SAS) AF: 0.352 AC: 1698 AN: 4820

European-Finnish (FIN) AF: 0.420 AC: 4432 AN: 10546

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23709 AN: 67916

Other (OTH) AF: 0.357 AC: 752 AN: 2106

Alfa AF: 0.365 Hom.: 1316

Bravo AF: 0.372

Asia WGS AF: 0.264 AC: 919 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.99
DANN	Benign	0.23
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1817074; hg19: chr7-50574012;