chr7-50461686-A-G

Variant names:

• chr7-50461686-A-G
• rs2060762
• NM_001082971.2:c.*18+1527T>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.*18+1527T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 152,204 control chromosomes in the GnomAD database, including 50,013 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 0.81 (50013 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.412
• Publications: 22 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.*18+1527T>C		intron_variant	Intron 14 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.*18+1527T>C		intron_variant	Intron 14 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.809 AC: 122966 AN: 152086 Hom.: 49960 Cov.: 33

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.822

Gnomad OTH AF: 0.818

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

GnomAD4 genome AF: 0.809 AC: 123078 AN: 152204 Hom.: 50013 Cov.: 33 AF XY: 0.810 AC XY: 60273 AN XY: 74422

African (AFR) AF: 0.792 AC: 32890 AN: 41520

American (AMR) AF: 0.868 AC: 13277 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2876 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2954 AN: 5166

South Asian (SAS) AF: 0.723 AC: 3490 AN: 4826

European-Finnish (FIN) AF: 0.850 AC: 9004 AN: 10590

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.822 AC: 55904 AN: 68018

Other (OTH) AF: 0.816 AC: 1721 AN: 2108

Alfa AF: 0.821 Hom.: 119541

Bravo AF: 0.811

Asia WGS AF: 0.678 AC: 2358 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.1
DANN	Benign	0.25
PhyloP100		-0.41
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: rs2060762; hg19: chr7-50529384;