rs7786398

Variant names:

• chr7-50545208-G-A
• rs7786398
• NM_001082971.2:c.-28-1095C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-50545208-G-A
• chr7-50545208-G-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.-28-1095C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 152,072 control chromosomes in the GnomAD database, including 20,450 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 0.51 (20450 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190
• 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: Labcorp Genetics (formerly Invitae), ClinGen, G2P, Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 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.-28-1095C>T		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.-28-1095C>T		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.-28-1095C>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.-28-1095C>T		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.-28-1095C>T		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.-28-1095C>T		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78200 AN: 151954 Hom.: 20424 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.655

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.619

Gnomad EAS AF: 0.529

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.449

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.515 AC: 78257 AN: 152072 Hom.: 20450 Cov.: 33 AF XY: 0.510 AC XY: 37886 AN XY: 74344

African (AFR) AF: 0.454 AC: 18798 AN: 41446

American (AMR) AF: 0.609 AC: 9305 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.619 AC: 2149 AN: 3470

East Asian (EAS) AF: 0.529 AC: 2737 AN: 5170

South Asian (SAS) AF: 0.409 AC: 1973 AN: 4822

European-Finnish (FIN) AF: 0.449 AC: 4749 AN: 10580

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36644 AN: 67986

Other (OTH) AF: 0.547 AC: 1154 AN: 2110

Alfa AF: 0.527 Hom.: 3640

Bravo AF: 0.526

Asia WGS AF: 0.512 AC: 1782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.5
DANN	Benign	0.70
PhyloP100		-0.019
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7786398;

hg19: chr7-50612906;