7-50498129-T-C

Variant names:

• chr7-50498129-T-C
• rs2167364
• NM_001082971.2:c.876+1019A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):​c.876+1019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 152,140 control chromosomes in the GnomAD database, including 6,958 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.30 (6958 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 16 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.876+1019A>G		intron_variant	Intron 8 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.876+1019A>G		intron_variant	Intron 8 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45136 AN: 152022 Hom.: 6958 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.322

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.297 AC: 45137 AN: 152140 Hom.: 6958 Cov.: 33 AF XY: 0.302 AC XY: 22479 AN XY: 74372

African (AFR) AF: 0.253 AC: 10486 AN: 41514

American (AMR) AF: 0.295 AC: 4518 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 926 AN: 3464

East Asian (EAS) AF: 0.117 AC: 608 AN: 5178

South Asian (SAS) AF: 0.323 AC: 1559 AN: 4820

European-Finnish (FIN) AF: 0.396 AC: 4183 AN: 10570

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.322 AC: 21880 AN: 67982

Other (OTH) AF: 0.286 AC: 604 AN: 2110

Alfa AF: 0.307 Hom.: 11413

Bravo AF: 0.286

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.045
DANN	Benign	0.23
PhyloP100		-1.6
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: rs2167364; hg19: chr7-50565827;