Genetic Variant PDSS2:c.*544dupT (chr6-107154074-T-TA) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020381.4(PDSS2):c.*544dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,770 control chromosomes in the GnomAD database, including 4,695 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.23 ( 4672 hom., cov: 26)

Exomes 𝑓: 0.18 ( 23 hom. )

Consequence

PDSS2
NM_020381.4 3_prime_UTR

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

Publications

1 publications found

Variant links:

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

PDSS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 6-107154074-T-TA is Benign according to our data. Variant chr6-107154074-T-TA is described in ClinVar as [Likely_benign]. Clinvar id is 354761.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS2	NM_020381.4 link	c.*544dupT		3_prime_UTR_variant	Exon 8 of 8	ENST00000369037.9	NP_065114.3	Q86YH6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS2	ENST00000369037.9 link	c.*544dupT		3_prime_UTR_variant	Exon 8 of 8	1	NM_020381.4	ENSP00000358033.4		Q86YH6-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

33766

AN:

149516

Hom.:

4672

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0574

Gnomad AMI

AF:

0.394

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.236

Gnomad SAS

AF:

0.242

Gnomad FIN

AF:

0.402

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.182

AC:

575

AN:

3162

Hom.:

Cov.:

AF XY:

0.177

AC XY:

299

AN XY:

1692

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.105

AC:

AN:

562

Ashkenazi Jewish (ASJ)

AF:

0.100

AC:

AN:

East Asian (EAS)

AF:

0.144

AC:

AN:

South Asian (SAS)

AF:

0.150

AC:

AN:

266

European-Finnish (FIN)

AF:

0.281

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.208

AC:

434

AN:

2086

Other (OTH)

AF:

0.194

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

124

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

33763

AN:

149608

Hom.:

4672

Cov.:

AF XY:

0.229

AC XY:

16714

AN XY:

72958

show subpopulations

African (AFR)

AF:

0.0573

AC:

2335

AN:

40746

American (AMR)

AF:

0.206

AC:

3072

AN:

14924

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

748

AN:

3454

East Asian (EAS)

AF:

0.237

AC:

1211

AN:

5120

South Asian (SAS)

AF:

0.244

AC:

1156

AN:

4738

European-Finnish (FIN)

AF:

0.402

AC:

4062

AN:

10094

Middle Eastern (MID)

AF:

0.207

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.302

AC:

20329

AN:

67296

Other (OTH)

AF:

0.213

AC:

437

AN:

2050

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

1183

2367

3550

4734

5917

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.134

Hom.:

273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Coenzyme Q10 deficiency

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.062

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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6-107154074-TAA-TAAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over