rs11575319

Variant names:

• chr7-50537799-G-A
• rs11575319
• NM_001082971.2:c.435+61C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001082971.2(DDC):​c.435+61C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,608,648 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0098 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.68
• Publications: 1 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 7-50537799-G-A is Benign according to our data. Variant chr7-50537799-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1678661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00983 (1496/152222) while in subpopulation AFR AF = 0.0344 (1428/41518). AF 95% confidence interval is 0.0329. There are 23 homozygotes in GnomAd4. There are 745 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 23 AR gene

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.435+61C>T		intron	N/A	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.435+61C>T		intron	N/A	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.321+61C>T		intron	N/A	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.435+61C>T		intron	N/A	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.435+61C>T		intron	N/A	ENSP00000350616.5	P20711-1
	DDC	ENST00000380984.4	TSL:1	c.435+61C>T		intron	N/A	ENSP00000370371.4	P20711-2

Frequencies

GnomAD3 genomes AF: 0.00982 AC: 1493 AN: 152104 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0344

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00321

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00526

GnomAD4 exome AF: 0.00106 AC: 1544 AN: 1456426 Hom.: 24 AF XY: 0.000928 AC XY: 673 AN XY: 724912

African (AFR) AF: 0.0356 AC: 1189 AN: 33358

American (AMR) AF: 0.00154 AC: 69 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000697 AC: 6 AN: 86132

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53366

Middle Eastern (MID) AF: 0.00209 AC: 12 AN: 5748

European-Non Finnish (NFE) AF: 0.000120 AC: 133 AN: 1107162

Other (OTH) AF: 0.00223 AC: 134 AN: 60182

GnomAD4 genome AF: 0.00983 AC: 1496 AN: 152222 Hom.: 23 Cov.: 32 AF XY: 0.0100 AC XY: 745 AN XY: 74444

African (AFR) AF: 0.0344 AC: 1428 AN: 41518

American (AMR) AF: 0.00320 AC: 49 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68012

Other (OTH) AF: 0.00520 AC: 11 AN: 2114

Alfa AF: 0.00575 Hom.: 6

Bravo AF: 0.0108

Asia WGS AF: 0.00231 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.016
DANN	Benign	0.65
PhyloP100		-1.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism

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: rs11575319; hg19: chr7-50605497;