chr7-50550562-G-A

Variant names:

• chr7-50550562-G-A
• rs11974297
• NM_001082971.2:c.-28-6449C>T

Variant summary

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

The NM_001082971.2(DDC):​c.-28-6449C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 152,014 control chromosomes in the GnomAD database, including 22,323 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 0.53 (22323 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.336
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-28-6449C>T		intron_variant	Intron 1 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-28-6449C>T		intron_variant	Intron 1 of 14	1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.531 AC: 80616 AN: 151894 Hom.: 22299 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.606

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.571

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.574

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

GnomAD4 genome AF: 0.531 AC: 80679 AN: 152014 Hom.: 22323 Cov.: 32 AF XY: 0.522 AC XY: 38774 AN XY: 74280

African (AFR) AF: 0.384 AC: 15911 AN: 41454

American (AMR) AF: 0.606 AC: 9253 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2276 AN: 3472

East Asian (EAS) AF: 0.480 AC: 2473 AN: 5156

South Asian (SAS) AF: 0.488 AC: 2348 AN: 4816

European-Finnish (FIN) AF: 0.453 AC: 4776 AN: 10546

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.613 AC: 41666 AN: 67988

Other (OTH) AF: 0.572 AC: 1205 AN: 2106

Alfa AF: 0.564 Hom.: 4307

Bravo AF: 0.536

Asia WGS AF: 0.527 AC: 1832 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.8
DANN	Benign	0.55
PhyloP100		0.34
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: rs11974297; hg19: chr7-50618260;