7-50556808-A-T

Variant names:

• chr7-50556808-A-T
• rs6969081
• NM_001082971.2:c.-29+8477T>A

Variant summary

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

The NM_001082971.2(DDC):​c.-29+8477T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 152,024 control chromosomes in the GnomAD database, including 17,924 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 0.47 (17924 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.329
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.626 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.-29+8477T>A		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.-29+4206T>A		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.-29+4206T>A		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.-29+8477T>A		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.-29+4206T>A		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.-29+4206T>A		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.471 AC: 71502 AN: 151906 Hom.: 17902 Cov.: 32

Gnomad AFR AF: 0.632

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.471 AC: 71567 AN: 152024 Hom.: 17924 Cov.: 32 AF XY: 0.478 AC XY: 35553 AN XY: 74308

African (AFR) AF: 0.632 AC: 26216 AN: 41480

American (AMR) AF: 0.373 AC: 5702 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1130 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2706 AN: 5164

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4820

European-Finnish (FIN) AF: 0.548 AC: 5778 AN: 10548

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26275 AN: 67954

Other (OTH) AF: 0.427 AC: 899 AN: 2106

Alfa AF: 0.275 Hom.: 616

Bravo AF: 0.463

Asia WGS AF: 0.472 AC: 1642 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	0.22
DANN	Benign	0.52
PhyloP100		-0.33
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: rs6969081; hg19: chr7-50624505;