Genetic Variant PAPSS2:c.-83_-75dupTGCTGCTGC (chr10-87659881-C-CGCTGCTGCT) – ACMG Classification: Benign (-10 pts)

Variant summary

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

The NM_001015880.2(PAPSS2):c.-83_-75dupTGCTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.042 ( 436 hom., cov: 0)

Exomes 𝑓: 0.0046 ( 98 hom. )

Consequence

PAPSS2
NM_001015880.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0360

Publications

2 publications found

Variant links:

Genes affected

PAPSS2 (HGNC:8604): (3'-phosphoadenosine 5'-phosphosulfate synthase 2) Sulfation is a common modification of endogenous (lipids, proteins, and carbohydrates) and exogenous (xenobiotics and drugs) compounds. In mammals, the sulfate source is 3'-phosphoadenosine 5'-phosphosulfate (PAPS), created from ATP and inorganic sulfate. Two different tissue isoforms encoded by different genes synthesize PAPS. This gene encodes one of the two PAPS synthetases. Defects in this gene cause the Pakistani type of spondyloepimetaphyseal dysplasia. Two alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]

PAPSS2 Gene-Disease associations (from GenCC):

spondyloepimetaphyseal dysplasia, PAPSS2 type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
autosomal recessive brachyolmia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PAPSS2 links:

ENSG00000196566 (HGNC:):

ENSG00000196566 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 10-87659881-C-CGCTGCTGCT is Benign according to our data. Variant chr10-87659881-C-CGCTGCTGCT is described in ClinVar as [Benign]. Clinvar id is 1274995.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2 link	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1	O95340-2
PAPSS2	NM_004670.4 link	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 12		NP_004661.2	O95340-1Q5TB52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2 link	c.-83_-75dupTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1		O95340-2

Frequencies

GnomAD3 genomes

AF:

0.0424

AC:

6408

AN:

151036

Hom.:

436

Cov.:

show subpopulations

Gnomad AFR

AF:

0.146

Gnomad AMI

AF:

0.0298

Gnomad AMR

AF:

0.0165

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00125

Gnomad FIN

AF:

0.0000956

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000887

Gnomad OTH

AF:

0.0272

GnomAD4 exome

AF:

0.00463

AC:

4106

AN:

886490

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

1805

AN XY:

460136

show subpopulations

African (AFR)

AF:

0.135

AC:

2957

AN:

21910

American (AMR)

AF:

0.00807

AC:

318

AN:

39404

Ashkenazi Jewish (ASJ)

AF:

0.000228

AC:

AN:

21948

East Asian (EAS)

AF:

0.0000287

AC:

AN:

34844

South Asian (SAS)

AF:

0.000583

AC:

AN:

72014

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46760

Middle Eastern (MID)

AF:

0.00812

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.000459

AC:

277

AN:

604094

Other (OTH)

AF:

0.0114

AC:

470

AN:

41080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

174

348

523

697

871

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0425

AC:

6416

AN:

151140

Hom.:

436

Cov.:

AF XY:

0.0411

AC XY:

3034

AN XY:

73864

show subpopulations

African (AFR)

AF:

0.146

AC:

6012

AN:

41208

American (AMR)

AF:

0.0164

AC:

250

AN:

15208

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00125

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0000956

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000888

AC:

AN:

67602

Other (OTH)

AF:

0.0269

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

259

518

776

1035

1294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.036

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-87659881-C-CGCTGCTGCT

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