rs11238131

Variant names:

• chr7-50470891-T-C
• rs11238131
• NM_001082971.2:c.1042-720A>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.1042-720A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 152,038 control chromosomes in the GnomAD database, including 33,569 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 0.66 (33569 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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: 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 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.1042-720A>G		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.1042-720A>G		intron	N/A	NP_000781.2
	DDC	NM_001242886.2		c.928-720A>G		intron	N/A	NP_001229815.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.1042-720A>G		intron	N/A	ENSP00000403644.2
	DDC	ENST00000357936.9	TSL:1	c.1042-720A>G		intron	N/A	ENSP00000350616.5
	DDC	ENST00000897740.1		c.1186-720A>G		intron	N/A	ENSP00000567799.1

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100484 AN: 151920 Hom.: 33523 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.735

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.662 AC: 100595 AN: 152038 Hom.: 33569 Cov.: 32 AF XY: 0.666 AC XY: 49459 AN XY: 74316

African (AFR) AF: 0.599 AC: 24833 AN: 41446

American (AMR) AF: 0.736 AC: 11262 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3470

East Asian (EAS) AF: 0.502 AC: 2597 AN: 5170

South Asian (SAS) AF: 0.631 AC: 3040 AN: 4818

European-Finnish (FIN) AF: 0.752 AC: 7959 AN: 10578

Middle Eastern (MID) AF: 0.565 AC: 166 AN: 294

European-Non Finnish (NFE) AF: 0.684 AC: 46486 AN: 67938

Other (OTH) AF: 0.658 AC: 1388 AN: 2108

Alfa AF: 0.674 Hom.: 97552

Bravo AF: 0.656

Asia WGS AF: 0.613 AC: 2131 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.43
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: rs11238131; hg19: chr7-50538589;