NM_001082971.2:c.714+4445C>T

Variant names:

• chr7-50523692-G-A
• rs10249982
• NM_001082971.2:c.714+4445C>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.714+4445C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 152,074 control chromosomes in the GnomAD database, including 40,544 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 0.73 (40544 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 7 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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.714+4445C>T		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.714+4445C>T		intron_variant	Intron 6 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110558 AN: 151956 Hom.: 40512 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.760

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.728 AC: 110637 AN: 152074 Hom.: 40544 Cov.: 33 AF XY: 0.716 AC XY: 53230 AN XY: 74324

African (AFR) AF: 0.720 AC: 29879 AN: 41474

American (AMR) AF: 0.616 AC: 9424 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3472

East Asian (EAS) AF: 0.796 AC: 4118 AN: 5174

South Asian (SAS) AF: 0.693 AC: 3340 AN: 4818

European-Finnish (FIN) AF: 0.640 AC: 6752 AN: 10546

Middle Eastern (MID) AF: 0.786 AC: 231 AN: 294

European-Non Finnish (NFE) AF: 0.760 AC: 51690 AN: 67980

Other (OTH) AF: 0.745 AC: 1574 AN: 2112

Alfa AF: 0.744 Hom.: 5451

Bravo AF: 0.727

Asia WGS AF: 0.765 AC: 2661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.65
DANN	Benign	0.14
PhyloP100		-1.2
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: rs10249982; hg19: chr7-50591390;