7-50484454-G-C

Variant names:

• chr7-50484454-G-C
• rs2122822
• NM_001082971.2:c.945-4591C>G

Variant summary

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

The NM_001082971.2(DDC):​c.945-4591C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 151,934 control chromosomes in the GnomAD database, including 23,298 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 0.55 (23298 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.520
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.609 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.945-4591C>G		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.945-4591C>G		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.831-4591C>G		intron	N/A	NP_001229815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.945-4591C>G		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.945-4591C>G		intron	N/A	ENSP00000350616.5
	DDC	ENST00000622873.4	TSL:3	c.831-4591C>G		intron	N/A	ENSP00000479110.1

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83710 AN: 151816 Hom.: 23256 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.571

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

GnomAD4 genome AF: 0.552 AC: 83814 AN: 151934 Hom.: 23298 Cov.: 33 AF XY: 0.547 AC XY: 40608 AN XY: 74248

African (AFR) AF: 0.523 AC: 21652 AN: 41430

American (AMR) AF: 0.620 AC: 9462 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2129 AN: 3468

East Asian (EAS) AF: 0.447 AC: 2305 AN: 5160

South Asian (SAS) AF: 0.514 AC: 2477 AN: 4818

European-Finnish (FIN) AF: 0.480 AC: 5052 AN: 10516

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38983 AN: 67960

Other (OTH) AF: 0.570 AC: 1203 AN: 2110

Alfa AF: 0.551 Hom.: 2859

Bravo AF: 0.558

Asia WGS AF: 0.528 AC: 1836 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.54
PhyloP100		-0.52
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: rs2122822; hg19: chr7-50552152;