7-50493846-G-A

Variant names:

• chr7-50493846-G-A
• rs7790758
• NM_001082971.2:c.944+1504C>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.944+1504C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 151,832 control chromosomes in the GnomAD database, including 45,366 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 0.77 (45366 hom., cov: 30)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.338
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.823 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.944+1504C>T		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.944+1504C>T		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.830+1504C>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.944+1504C>T		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.944+1504C>T		intron	N/A	ENSP00000350616.5
	DDC	ENST00000380984.4	TSL:1	c.945-841C>T		intron	N/A	ENSP00000370371.4

Frequencies

GnomAD3 genomes AF: 0.771 AC: 116961 AN: 151714 Hom.: 45310 Cov.: 30

Gnomad AFR AF: 0.758

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.800

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.771 AC: 117077 AN: 151832 Hom.: 45366 Cov.: 30 AF XY: 0.772 AC XY: 57279 AN XY: 74204

African (AFR) AF: 0.759 AC: 31403 AN: 41382

American (AMR) AF: 0.835 AC: 12761 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 2778 AN: 3472

East Asian (EAS) AF: 0.558 AC: 2877 AN: 5152

South Asian (SAS) AF: 0.701 AC: 3371 AN: 4810

European-Finnish (FIN) AF: 0.798 AC: 8383 AN: 10504

Middle Eastern (MID) AF: 0.701 AC: 206 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 53003 AN: 67922

Other (OTH) AF: 0.772 AC: 1630 AN: 2112

Alfa AF: 0.768 Hom.: 5810

Bravo AF: 0.773

Asia WGS AF: 0.662 AC: 2303 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.72
DANN	Benign	0.27
PhyloP100		-0.34
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: rs7790758; hg19: chr7-50561544;