chr7-50467697-C-T

Variant names:

• chr7-50467697-C-T
• rs11575522
• NM_001082971.2:c.1141-382G>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.1141-382G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0526 in 152,294 control chromosomes in the GnomAD database, including 491 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 0.053 (491 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.22
• Publications: 12 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 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.1141-382G>A		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.1141-382G>A		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.1027-382G>A		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.1141-382G>A		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.1141-382G>A		intron	N/A	ENSP00000350616.5
	DDC	ENST00000622873.4	TSL:3	c.1027-382G>A		intron	N/A	ENSP00000479110.1

Frequencies

GnomAD3 genomes AF: 0.0524 AC: 7979 AN: 152176 Hom.: 486 Cov.: 33

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0285

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00753

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0526 AC: 8014 AN: 152294 Hom.: 491 Cov.: 33 AF XY: 0.0506 AC XY: 3770 AN XY: 74466

African (AFR) AF: 0.148 AC: 6166 AN: 41538

American (AMR) AF: 0.0285 AC: 436 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4832

European-Finnish (FIN) AF: 0.00753 AC: 80 AN: 10620

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0168 AC: 1140 AN: 68018

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0285 Hom.: 523

Bravo AF: 0.0580

Asia WGS AF: 0.0140 AC: 49 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.052
DANN	Benign	0.54
PhyloP100		-5.2
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: rs11575522; hg19: chr7-50535395;