7-50463171-G-A

Position:

• chr7-50463171-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.*18+42C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,511,196 control chromosomes in the GnomAD database, including 1,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.051 (437 hom., cov: 32)
  • Exomes 𝑓: 0.018 (575 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.10

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 7-50463171-G-A is Benign according to our data. Variant chr7-50463171-G-A is described in ClinVar as [Benign]. Clinvar id is 1222837.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.*18+42C>T		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.*18+42C>T		intron_variant		1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.0505 AC: 7678 AN: 152134 Hom.: 433 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0273

Gnomad ASJ AF: 0.00779

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.00763

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0167

Gnomad OTH AF: 0.0369

GnomAD4 exome AF: 0.0184 AC: 25051 AN: 1358944 Hom.: 575 Cov.: 24 AF XY: 0.0179 AC XY: 12036 AN XY: 673112

Gnomad4 AFR exome AF: 0.148

Gnomad4 AMR exome AF: 0.0142

Gnomad4 ASJ exome AF: 0.00844

Gnomad4 EAS exome AF: 0.0000558

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.00930

Gnomad4 NFE exome AF: 0.0161

Gnomad4 OTH exome AF: 0.0237

GnomAD4 genome AF: 0.0507 AC: 7712 AN: 152252 Hom.: 437 Cov.: 32 AF XY: 0.0487 AC XY: 3627 AN XY: 74450

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.0273

Gnomad4 ASJ AF: 0.00779

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0141

Gnomad4 FIN AF: 0.00763

Gnomad4 NFE AF: 0.0167

Gnomad4 OTH AF: 0.0366

Alfa AF: 0.0188 Hom.: 62

Bravo AF: 0.0557

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs11575543; hg19: chr7-50530869;