rs11575543

Variant names:

• chr7-50463171-G-A
• rs11575543
• NM_001082971.2:c.*18+42C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-50463171-G-A
• chr7-50463171-G-T

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.*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
• Publications: 10 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 -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 VariationId 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 rank	MANE	Protein	UniProt
DDC	NM_001082971.2	c.*18+42C>T		intron_variant	Intron 14 of 14	ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.*18+42C>T		intron_variant	Intron 14 of 14	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

African (AFR) AF: 0.148 AC: 4549 AN: 30798

American (AMR) AF: 0.0142 AC: 512 AN: 36094

Ashkenazi Jewish (ASJ) AF: 0.00844 AC: 211 AN: 24986

East Asian (EAS) AF: 0.0000558 AC: 2 AN: 35846

South Asian (SAS) AF: 0.0141 AC: 1111 AN: 78652

European-Finnish (FIN) AF: 0.00930 AC: 446 AN: 47942

Middle Eastern (MID) AF: 0.0140 AC: 57 AN: 4076

European-Non Finnish (NFE) AF: 0.0161 AC: 16821 AN: 1043930

Other (OTH) AF: 0.0237 AC: 1342 AN: 56620

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

African (AFR) AF: 0.142 AC: 5885 AN: 41530

American (AMR) AF: 0.0273 AC: 418 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00779 AC: 27 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4828

European-Finnish (FIN) AF: 0.00763 AC: 81 AN: 10612

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0167 AC: 1137 AN: 68022

Other (OTH) AF: 0.0366 AC: 77 AN: 2106

Alfa AF: 0.0250 Hom.: 143

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

Apr 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.56
DANN	Benign	0.27
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs11575543; hg19: chr7-50530869;