dbSNP rs17124941: PAPSS2:p.Ser92Ser (chr10-87713205-T-C) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001015880.2(PAPSS2):c.276T>C(p.Ser92Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00327 in 1,609,440 control chromosomes in the GnomAD database, including 111 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0033 ( 8 hom., cov: 28)

Exomes 𝑓: 0.0033 ( 103 hom. )

Consequence

PAPSS2
NM_001015880.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.249

Publications

4 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 10-87713205-T-C is Benign according to our data. Variant chr10-87713205-T-C is described in ClinVar as Benign. ClinVar VariationId is 537718.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.249 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00331 (494/149136) while in subpopulation EAS AF = 0.0389 (193/4960). AF 95% confidence interval is 0.0344. There are 8 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001015880.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS2	NM_001015880.2	MANE Select	c.276T>C	p.Ser92Ser	synonymous	Exon 3 of 13	NP_001015880.1
	PAPSS2	NM_004670.4		c.276T>C	p.Ser92Ser	synonymous	Exon 3 of 12	NP_004661.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PAPSS2	ENST00000456849.2	TSL:1 MANE Select	c.276T>C	p.Ser92Ser	synonymous	Exon 3 of 13	ENSP00000406157.1
PAPSS2	ENST00000361175.8	TSL:1	c.276T>C	p.Ser92Ser	synonymous	Exon 3 of 12	ENSP00000354436.4
PAPSS2	ENST00000482258.1	TSL:5	n.319T>C		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.00323

AC:

481

AN:

149020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000813

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0390

Gnomad SAS

AF:

0.0304

Gnomad FIN

AF:

0.00290

Gnomad MID

AF:

0.00662

Gnomad NFE

AF:

0.000680

Gnomad OTH

AF:

0.00439

GnomAD2 exomes

AF:

0.00617

AC:

1550

AN:

251302

AF XY:

0.00692

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0327

Gnomad FIN exome

AF:

0.00222

Gnomad NFE exome

AF:

0.00117

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00326

AC:

4761

AN:

1460304

Hom.:

103

Cov.:

AF XY:

0.00386

AC XY:

2801

AN XY:

726496

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

33414

American (AMR)

AF:

0.000515

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.0482

AC:

1908

AN:

39624

South Asian (SAS)

AF:

0.0209

AC:

1806

AN:

86230

European-Finnish (FIN)

AF:

0.00212

AC:

113

AN:

53252

Middle Eastern (MID)

AF:

0.00382

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000519

AC:

577

AN:

1110944

Other (OTH)

AF:

0.00431

AC:

260

AN:

60304

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

256

511

767

1022

1278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00331

AC:

494

AN:

149136

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

284

AN XY:

72658

show subpopulations

African (AFR)

AF:

0.00124

AC:

AN:

40408

American (AMR)

AF:

0.000813

AC:

AN:

14768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.0389

AC:

193

AN:

4960

South Asian (SAS)

AF:

0.0302

AC:

140

AN:

4632

European-Finnish (FIN)

AF:

0.00290

AC:

AN:

10000

Middle Eastern (MID)

AF:

0.00709

AC:

AN:

282

European-Non Finnish (NFE)

AF:

0.000680

AC:

AN:

67642

Other (OTH)

AF:

0.0106

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00103

Hom.:

Bravo

AF:

0.00244

Asia WGS

AF:

0.0370

AC:

129

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Spondyloepimetaphyseal dysplasia, PAPSS2 type

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.7

(source)

DANN

Benign

0.66

PhyloP100

-0.25

Mutation Taster

=100/0

polymorphism

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over