6-107232108-C-T

Variant names:

• chr6-107232108-C-T
• rs2216084
• NM_020381.4:c.702+13440G>A

Variant summary

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

The NM_020381.4(PDSS2):​c.702+13440G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,164 control chromosomes in the GnomAD database, including 45,383 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 0.76 (45383 hom., cov: 33)
• Consequence: PDSS2 NM_020381.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 5 publications found

Genes affected

PDSS2 (HGNC:23041): (decaprenyl diphosphate synthase subunit 2) The protein encoded by this gene is an enzyme that synthesizes the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. Defects in this gene are a cause of coenzyme Q10 deficiency.[provided by RefSeq, Oct 2009]

PDSS2 Gene-Disease associations (from GenCC):

• coenzyme Q10 deficiency, primary, 3

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Leigh syndrome

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• Leigh syndrome with nephrotic syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4	c.702+13440G>A		intron_variant	Intron 4 of 7	ENST00000369037.9	NP_065114.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9	c.702+13440G>A		intron_variant	Intron 4 of 7	1	NM_020381.4	ENSP00000358033.4

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115536 AN: 152046 Hom.: 45321 Cov.: 33

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.647

Gnomad EAS AF: 0.995

Gnomad SAS AF: 0.812

Gnomad FIN AF: 0.766

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.760 AC: 115655 AN: 152164 Hom.: 45383 Cov.: 33 AF XY: 0.766 AC XY: 56959 AN XY: 74374

African (AFR) AF: 0.935 AC: 38833 AN: 41524

American (AMR) AF: 0.721 AC: 11018 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.647 AC: 2246 AN: 3470

East Asian (EAS) AF: 0.995 AC: 5167 AN: 5192

South Asian (SAS) AF: 0.811 AC: 3911 AN: 4820

European-Finnish (FIN) AF: 0.766 AC: 8112 AN: 10584

Middle Eastern (MID) AF: 0.531 AC: 155 AN: 292

European-Non Finnish (NFE) AF: 0.648 AC: 44080 AN: 67986

Other (OTH) AF: 0.717 AC: 1513 AN: 2110

Alfa AF: 0.713 Hom.: 4902

Bravo AF: 0.763

Asia WGS AF: 0.919 AC: 3193 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.4
DANN	Benign	0.76
PhyloP100		-1.2
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: rs2216084; hg19: chr6-107553312;