7-50539508-A-G

Position:

• chr7-50539508-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082971.2(DDC):​c.315+407T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.904 in 152,236 control chromosomes in the GnomAD database, including 62,302 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.90 (62302 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0460

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-AS1 (HGNC:40171): (DDC antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BP6: Variant 7-50539508-A-G is Benign according to our data. Variant chr7-50539508-A-G is described in ClinVar as [Benign]. Clinvar id is 3256803.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.315+407T>C		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.315+407T>C		intron_variant		1	NM_001082971.2	ENSP00000403644.2

Frequencies

GnomAD3 genomes AF: 0.904 AC: 137545 AN: 152118 Hom.: 62256 Cov.: 31

Gnomad AFR AF: 0.917

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.884

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.904 AC: 137652 AN: 152236 Hom.: 62302 Cov.: 31 AF XY: 0.906 AC XY: 67429 AN XY: 74424

Gnomad4 AFR AF: 0.917

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.916

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.885

Gnomad4 FIN AF: 0.922

Gnomad4 NFE AF: 0.884

Gnomad4 OTH AF: 0.902

Alfa AF: 0.889 Hom.: 11746

Bravo AF: 0.906

Asia WGS AF: 0.936 AC: 3257 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jul 31, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 99% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 92. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.3
DANN	Benign	0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1466163; hg19: chr7-50607206;