chr7-50509205-G-A

Variant names:

• chr7-50509205-G-A
• rs7808025
• NM_001082971.2:c.715-5146C>T

Variant summary

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

The NM_001082971.2(DDC):​c.715-5146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 151,642 control chromosomes in the GnomAD database, including 6,262 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 0.28 (6262 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572
• Publications: 8 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: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.715-5146C>T		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.715-5146C>T		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.601-5146C>T		intron	N/A	NP_001229815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.715-5146C>T		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.715-5146C>T		intron	N/A	ENSP00000350616.5
	DDC	ENST00000380984.4	TSL:1	c.715-5146C>T		intron	N/A	ENSP00000370371.4

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41865 AN: 151524 Hom.: 6236 Cov.: 31

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.277 AC: 41940 AN: 151642 Hom.: 6262 Cov.: 31 AF XY: 0.285 AC XY: 21070 AN XY: 74054

African (AFR) AF: 0.366 AC: 15097 AN: 41304

American (AMR) AF: 0.340 AC: 5185 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 686 AN: 3468

East Asian (EAS) AF: 0.197 AC: 1013 AN: 5154

South Asian (SAS) AF: 0.231 AC: 1105 AN: 4778

European-Finnish (FIN) AF: 0.342 AC: 3576 AN: 10468

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.214 AC: 14521 AN: 67912

Other (OTH) AF: 0.250 AC: 528 AN: 2112

Alfa AF: 0.267 Hom.: 985

Bravo AF: 0.280

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.69
DANN	Benign	0.55
PhyloP100		-0.57
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: rs7808025; hg19: chr7-50576903;