NM_001082971.2:c.715-1133C>T

Variant names:

• chr7-50505192-G-A
• rs6592961
• NM_001082971.2:c.715-1133C>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.715-1133C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 152,036 control chromosomes in the GnomAD database, including 6,295 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 0.28 (6295 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 19 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 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.715-1133C>T		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.715-1133C>T		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.601-1133C>T		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.715-1133C>T		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.715-1133C>T		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.715-1133C>T		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.276 AC: 41934 AN: 151918 Hom.: 6269 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.247

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

GnomAD4 genome AF: 0.276 AC: 42013 AN: 152036 Hom.: 6295 Cov.: 33 AF XY: 0.284 AC XY: 21121 AN XY: 74290

African (AFR) AF: 0.366 AC: 15160 AN: 41468

American (AMR) AF: 0.344 AC: 5253 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.196 AC: 1014 AN: 5162

South Asian (SAS) AF: 0.216 AC: 1040 AN: 4814

European-Finnish (FIN) AF: 0.340 AC: 3588 AN: 10548

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14496 AN: 67974

Other (OTH) AF: 0.248 AC: 522 AN: 2108

Alfa AF: 0.230 Hom.: 18391

Bravo AF: 0.281

Asia WGS AF: 0.195 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.056
DANN	Benign	0.42
PhyloP100		-2.0
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: rs6592961; hg19: chr7-50572890;