7-50529166-C-T

Variant names:

• chr7-50529166-C-T
• rs3735273
• NM_001082971.2:c.570+42G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.570+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,610,546 control chromosomes in the GnomAD database, including 49,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (5918 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43341 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.48
• Publications: 32 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-50529166-C-T is Benign according to our data. Variant chr7-50529166-C-T is described in ClinVar as Benign. ClinVar VariationId is 1256784.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.570+42G>A		intron_variant	Intron 5 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.570+42G>A		intron_variant	Intron 5 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40997 AN: 151902 Hom.: 5907 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.246 AC: 61918 AN: 251274 AF XY: 0.252

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.239 AC: 349002 AN: 1458528 Hom.: 43341 Cov.: 32 AF XY: 0.242 AC XY: 175589 AN XY: 725654

African (AFR) AF: 0.363 AC: 12105 AN: 33374

American (AMR) AF: 0.124 AC: 5558 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.197 AC: 5141 AN: 26130

East Asian (EAS) AF: 0.381 AC: 15114 AN: 39686

South Asian (SAS) AF: 0.315 AC: 27080 AN: 86100

European-Finnish (FIN) AF: 0.217 AC: 11608 AN: 53408

Middle Eastern (MID) AF: 0.276 AC: 1173 AN: 4248

European-Non Finnish (NFE) AF: 0.230 AC: 255841 AN: 1110710

Other (OTH) AF: 0.256 AC: 15382 AN: 60158

GnomAD4 genome AF: 0.270 AC: 41032 AN: 152018 Hom.: 5918 Cov.: 32 AF XY: 0.268 AC XY: 19915 AN XY: 74320

African (AFR) AF: 0.358 AC: 14847 AN: 41448

American (AMR) AF: 0.185 AC: 2827 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 706 AN: 3468

East Asian (EAS) AF: 0.396 AC: 2035 AN: 5144

South Asian (SAS) AF: 0.322 AC: 1550 AN: 4812

European-Finnish (FIN) AF: 0.209 AC: 2206 AN: 10572

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15971 AN: 67974

Other (OTH) AF: 0.258 AC: 543 AN: 2108

Alfa AF: 0.255 Hom.: 10072

Bravo AF: 0.271

Asia WGS AF: 0.333 AC: 1158 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Mar 26, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

Jul 31, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 35% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 33. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.72
DANN	Benign	0.51
PhyloP100		-2.5
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: rs3735273; hg19: chr7-50596864; COSMIC: COSV63567855; COSMIC: COSV63567855;