rs11575302

Variant names:

• chr7-50539996-G-A
• rs11575302
• NM_001082971.2:c.234C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001082971.2(DDC):​c.234C>T​(p.Ala78Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 1,613,830 control chromosomes in the GnomAD database, including 1,036 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (437 hom., cov: 32)
  • Exomes 𝑓: 0.018 (599 hom.)
• Consequence: DDC NM_001082971.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.901
• Publications: 11 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-AS1 (HGNC:40171): (DDC antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.074).
• BP6: Variant 7-50539996-G-A is Benign according to our data. Variant chr7-50539996-G-A is described in ClinVar as Benign. ClinVar VariationId is 360441.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.901 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 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.234C>T	p.Ala78Ala	synonymous	Exon 3 of 15	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.234C>T	p.Ala78Ala	synonymous	Exon 3 of 15	NP_000781.2	P20711-1
	DDC	NM_001242887.2		c.234C>T	p.Ala78Ala	synonymous	Exon 3 of 14	NP_001229816.2	A0A087WU57

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.234C>T	p.Ala78Ala	synonymous	Exon 3 of 15	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.234C>T	p.Ala78Ala	synonymous	Exon 3 of 15	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.234C>T	p.Ala78Ala	synonymous	Exon 3 of 10	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7528 AN: 152140 Hom.: 430 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0221

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00735

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0430

GnomAD2 exomes AF: 0.0215 AC: 5392 AN: 250550 AF XY: 0.0196

Gnomad AFR exome AF: 0.139

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.00904

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00803

Gnomad NFE exome AF: 0.0176

Gnomad OTH exome AF: 0.0154

GnomAD4 exome AF: 0.0184 AC: 26873 AN: 1461570 Hom.: 599 Cov.: 31 AF XY: 0.0178 AC XY: 12908 AN XY: 727082

African (AFR) AF: 0.146 AC: 4895 AN: 33450

American (AMR) AF: 0.0124 AC: 555 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00846 AC: 221 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.0144 AC: 1242 AN: 86222

European-Finnish (FIN) AF: 0.00892 AC: 476 AN: 53374

Middle Eastern (MID) AF: 0.0128 AC: 74 AN: 5768

European-Non Finnish (NFE) AF: 0.0162 AC: 18046 AN: 1111828

Other (OTH) AF: 0.0226 AC: 1362 AN: 60384

GnomAD4 genome AF: 0.0497 AC: 7564 AN: 152260 Hom.: 437 Cov.: 32 AF XY: 0.0478 AC XY: 3559 AN XY: 74454

African (AFR) AF: 0.140 AC: 5813 AN: 41518

American (AMR) AF: 0.0222 AC: 339 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00778 AC: 27 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0143 AC: 69 AN: 4830

European-Finnish (FIN) AF: 0.00735 AC: 78 AN: 10612

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0166 AC: 1131 AN: 68022

Other (OTH) AF: 0.0426 AC: 90 AN: 2114

Alfa AF: 0.0319 Hom.: 109

Bravo AF: 0.0546

Asia WGS AF: 0.0110 AC: 39 AN: 3478

EpiCase AF: 0.0154

EpiControl AF: 0.0165

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Deficiency of aromatic-L-amino-acid decarboxylase (2)
-	-	2	not provided (2)
-	-	1	DDC-related disorder (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11575302; hg19: chr7-50607694;