chr7-50476365-A-C

Variant names:

• chr7-50476365-A-C
• rs732215
• NM_001082971.2:c.1041+259T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082971.2(DDC):​c.1041+259T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 152,000 control chromosomes in the GnomAD database, including 14,035 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (14035 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.273
• Publications: 14 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 7-50476365-A-C is Benign according to our data. Variant chr7-50476365-A-C is described in ClinVar as Benign. ClinVar VariationId is 1239810.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.1041+259T>G		intron_variant	Intron 11 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.1041+259T>G		intron_variant	Intron 11 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64608 AN: 151882 Hom.: 14010 Cov.: 32

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.527

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.426 AC: 64678 AN: 152000 Hom.: 14035 Cov.: 32 AF XY: 0.426 AC XY: 31651 AN XY: 74292

African (AFR) AF: 0.346 AC: 14326 AN: 41464

American (AMR) AF: 0.524 AC: 8005 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 1830 AN: 3470

East Asian (EAS) AF: 0.465 AC: 2391 AN: 5146

South Asian (SAS) AF: 0.361 AC: 1743 AN: 4824

European-Finnish (FIN) AF: 0.458 AC: 4841 AN: 10572

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30125 AN: 67926

Other (OTH) AF: 0.446 AC: 941 AN: 2110

Alfa AF: 0.409 Hom.: 5676

Bravo AF: 0.429

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.87
CADD	Benign	0.42
DANN	Benign	0.79
PhyloP100		-0.27
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: rs732215; hg19: chr7-50544063;