NM_001082971.2:c.715-1576T>C

Variant names:

• chr7-50505635-A-G
• rs7809758
• NM_001082971.2:c.715-1576T>C

Variant summary

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

The NM_001082971.2(DDC):​c.715-1576T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.357 in 152,252 control chromosomes in the GnomAD database, including 9,971 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 0.36 (9971 hom., cov: 34)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0700
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.715-1576T>C		intron_variant	Intron 6 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.715-1576T>C		intron_variant	Intron 6 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.357 AC: 54285 AN: 152136 Hom.: 9952 Cov.: 34

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.353

Gnomad FIN AF: 0.420

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.345

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

GnomAD4 genome AF: 0.357 AC: 54345 AN: 152252 Hom.: 9971 Cov.: 34 AF XY: 0.364 AC XY: 27110 AN XY: 74442

African (AFR) AF: 0.350 AC: 14531 AN: 41532

American (AMR) AF: 0.441 AC: 6751 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1037 AN: 5182

South Asian (SAS) AF: 0.352 AC: 1697 AN: 4816

European-Finnish (FIN) AF: 0.420 AC: 4462 AN: 10618

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23725 AN: 68018

Other (OTH) AF: 0.345 AC: 727 AN: 2110

Alfa AF: 0.352 Hom.: 16134

Bravo AF: 0.356

Asia WGS AF: 0.262 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.41
DANN	Benign	0.37
PhyloP100		0.070
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: rs7809758; hg19: chr7-50573333;