7-50477395-T-C

Variant names:

• chr7-50477395-T-C
• rs3887825
• NM_001082971.2:c.1022-752A>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.1022-752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 152,012 control chromosomes in the GnomAD database, including 23,631 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 0.56 (23631 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.698
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.611 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.1022-752A>G		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.1022-752A>G		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.908-752A>G		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.1022-752A>G		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.1022-752A>G		intron	N/A	ENSP00000350616.5
	DDC	ENST00000622873.4	TSL:3	c.908-752A>G		intron	N/A	ENSP00000479110.1

Frequencies

GnomAD3 genomes AF: 0.555 AC: 84327 AN: 151894 Hom.: 23589 Cov.: 32

Gnomad AFR AF: 0.521

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.621

Gnomad ASJ AF: 0.615

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.513

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.555 AC: 84432 AN: 152012 Hom.: 23631 Cov.: 32 AF XY: 0.553 AC XY: 41054 AN XY: 74282

African (AFR) AF: 0.521 AC: 21611 AN: 41444

American (AMR) AF: 0.622 AC: 9503 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 2134 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2308 AN: 5156

South Asian (SAS) AF: 0.513 AC: 2469 AN: 4814

European-Finnish (FIN) AF: 0.531 AC: 5596 AN: 10548

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39042 AN: 67978

Other (OTH) AF: 0.575 AC: 1215 AN: 2112

Alfa AF: 0.558 Hom.: 4588

Bravo AF: 0.558

Asia WGS AF: 0.531 AC: 1848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.11
DANN	Benign	0.41
PhyloP100		-0.70
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: rs3887825; hg19: chr7-50545093;