rs998850

Variant names:

• chr7-50539690-G-C
• rs998850
• NM_001082971.2:c.315+225C>G

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.315+225C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 534,666 control chromosomes in the GnomAD database, including 60,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15231 hom., cov: 32)
  • Exomes 𝑓: 0.48 (45143 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0140
• Publications: 15 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=-0.89).
• BP6: Variant 7-50539690-G-C is Benign according to our data. Variant chr7-50539690-G-C is described in ClinVar as Benign. ClinVar VariationId is 1245436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.52 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.315+225C>G		intron_variant	Intron 3 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.315+225C>G		intron_variant	Intron 3 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66094 AN: 151922 Hom.: 15219 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.478 AC: 182929 AN: 382626 Hom.: 45143 AF XY: 0.472 AC XY: 96027 AN XY: 203466

African (AFR) AF: 0.286 AC: 3249 AN: 11350

American (AMR) AF: 0.420 AC: 9208 AN: 21936

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 7199 AN: 11702

East Asian (EAS) AF: 0.394 AC: 9165 AN: 23272

South Asian (SAS) AF: 0.367 AC: 17505 AN: 47724

European-Finnish (FIN) AF: 0.429 AC: 9567 AN: 22312

Middle Eastern (MID) AF: 0.526 AC: 841 AN: 1600

European-Non Finnish (NFE) AF: 0.523 AC: 115880 AN: 221442

Other (OTH) AF: 0.485 AC: 10315 AN: 21288

GnomAD4 genome AF: 0.435 AC: 66122 AN: 152040 Hom.: 15231 Cov.: 32 AF XY: 0.426 AC XY: 31662 AN XY: 74316

African (AFR) AF: 0.286 AC: 11866 AN: 41488

American (AMR) AF: 0.419 AC: 6400 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2129 AN: 3472

East Asian (EAS) AF: 0.401 AC: 2074 AN: 5170

South Asian (SAS) AF: 0.364 AC: 1750 AN: 4808

European-Finnish (FIN) AF: 0.430 AC: 4543 AN: 10560

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.525 AC: 35651 AN: 67964

Other (OTH) AF: 0.468 AC: 987 AN: 2110

Alfa AF: 0.471 Hom.: 2133

Bravo AF: 0.430

Asia WGS AF: 0.422 AC: 1472 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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 54% 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: 50. Only high quality variants are reported. -

not provided Benign:1

Mar 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.52
PhyloP100		0.014
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs998850; hg19: chr7-50607388;