Genetic Variant PAPSS2:c.-80_-75dupTGCTGC (chr10-87659881-C-CGCTGCT) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_001015880.2(PAPSS2):c.-80_-75dupTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.010 ( 26 hom., cov: 0)

Exomes 𝑓: 0.0025 ( 10 hom. )

Consequence

PAPSS2
NM_001015880.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0104 (1579/151164) while in subpopulation AFR AF = 0.0328 (1354/41228). AF 95% confidence interval is 0.0314. There are 26 homozygotes in GnomAd4. There are 731 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2 link	c.-80_-75dupTGCTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1	O95340-2
PAPSS2	NM_004670.4 link	c.-80_-75dupTGCTGC		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.-80_-75dupTGCTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1		O95340-2

Frequencies

GnomAD3 genomes

AF:

0.0104

AC:

1575

AN:

151060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0329

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00290

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000973

Gnomad SAS

AF:

0.00250

Gnomad FIN

AF:

0.00143

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.00826

GnomAD4 exome

AF:

0.00248

AC:

2195

AN:

886280

Hom.:

Cov.:

AF XY:

0.00234

AC XY:

1078

AN XY:

460036

show subpopulations

African (AFR)

AF:

0.0318

AC:

692

AN:

21732

American (AMR)

AF:

0.00238

AC:

AN:

39414

Ashkenazi Jewish (ASJ)

AF:

0.000501

AC:

AN:

21948

East Asian (EAS)

AF:

0.000373

AC:

AN:

34844

South Asian (SAS)

AF:

0.00161

AC:

116

AN:

72016

European-Finnish (FIN)

AF:

0.00175

AC:

AN:

46758

Middle Eastern (MID)

AF:

0.00564

AC:

AN:

4436

European-Non Finnish (NFE)

AF:

0.00167

AC:

1011

AN:

604064

Other (OTH)

AF:

0.00368

AC:

151

AN:

41068

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

104

208

312

416

520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0104

AC:

1579

AN:

151164

Hom.:

Cov.:

AF XY:

0.00989

AC XY:

731

AN XY:

73876

show subpopulations

African (AFR)

AF:

0.0328

AC:

1354

AN:

41228

American (AMR)

AF:

0.00289

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3456

East Asian (EAS)

AF:

0.000976

AC:

AN:

5124

South Asian (SAS)

AF:

0.00271

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00143

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00188

AC:

127

AN:

67604

Other (OTH)

AF:

0.00865

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000581

Hom.:

286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.036

Mutation Taster

=300/0

polymorphism

(source)

Splicing

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

Publications

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10-87659881-CGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over