7-50499795-G-A

Variant names:

• chr7-50499795-G-A
• rs6951648
• NM_001082971.2:c.782-553C>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.782-553C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,110 control chromosomes in the GnomAD database, including 2,885 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 0.19 (2885 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.203
• Publications: 10 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 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.782-553C>T		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.782-553C>T		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.668-553C>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.782-553C>T		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.782-553C>T		intron	N/A	ENSP00000350616.5
	DDC	ENST00000380984.4	TSL:1	c.782-553C>T		intron	N/A	ENSP00000370371.4

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29211 AN: 151992 Hom.: 2890 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0444

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.192 AC: 29208 AN: 152110 Hom.: 2885 Cov.: 32 AF XY: 0.190 AC XY: 14107 AN XY: 74372

African (AFR) AF: 0.220 AC: 9121 AN: 41486

American (AMR) AF: 0.178 AC: 2721 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 678 AN: 3470

East Asian (EAS) AF: 0.0441 AC: 228 AN: 5166

South Asian (SAS) AF: 0.204 AC: 981 AN: 4804

European-Finnish (FIN) AF: 0.133 AC: 1409 AN: 10606

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13457 AN: 67972

Other (OTH) AF: 0.190 AC: 402 AN: 2112

Alfa AF: 0.199 Hom.: 3886

Bravo AF: 0.194

Asia WGS AF: 0.122 AC: 425 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.64
PhyloP100		0.20
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: rs6951648; hg19: chr7-50567493;