rs45467596

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001015880.2(PAPSS2):c.886G>A(p.Val296Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.012 in 1,612,812 control chromosomes in the GnomAD database, including 141 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 5 hom., cov: 32)

Exomes 𝑓: 0.012 ( 136 hom. )

Consequence

PAPSS2
NM_001015880.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.13

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008572251).

BP6

Variant 10-87727289-G-A is Benign according to our data. Variant chr10-87727289-G-A is described in ClinVar as [Benign]. Clinvar id is 500278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87727289-G-A is described in Lovd as [Likely_benign]. Variant chr10-87727289-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00845 (1286/152278) while in subpopulation NFE AF= 0.0142 (966/68018). AF 95% confidence interval is 0.0135. There are 5 homozygotes in gnomad4. There are 589 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2 link	c.886G>A	p.Val296Met	missense_variant	Exon 9 of 13	ENST00000456849.2	NP_001015880.1	O95340-2
PAPSS2	NM_004670.4 link	c.871G>A	p.Val291Met	missense_variant	Exon 8 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.886G>A	p.Val296Met	missense_variant	Exon 9 of 13	1	NM_001015880.2	ENSP00000406157.1		O95340-2
PAPSS2	ENST00000361175.8 link	c.871G>A	p.Val291Met	missense_variant	Exon 8 of 12	1		ENSP00000354436.4		O95340-1

Frequencies

GnomAD3 genomes

AF:

0.00845

AC:

1286

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00261

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.00891

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000943

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0142

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.00815

AC:

2046

AN:

250964

Hom.:

AF XY:

0.00835

AC XY:

1132

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.00252

Gnomad AMR exome

AF:

0.00665

Gnomad ASJ exome

AF:

0.00766

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00118

Gnomad FIN exome

AF:

0.00102

Gnomad NFE exome

AF:

0.0139

Gnomad OTH exome

AF:

0.0106

GnomAD4 exome

AF:

0.0123

AC:

18002

AN:

1460534

Hom.:

136

Cov.:

AF XY:

0.0121

AC XY:

8797

AN XY:

726628

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.00671

Gnomad4 ASJ exome

AF:

0.00739

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00160

Gnomad4 FIN exome

AF:

0.00133

Gnomad4 NFE exome

AF:

0.0149

Gnomad4 OTH exome

AF:

0.00936

GnomAD4 genome

AF:

0.00845

AC:

1286

AN:

152278

Hom.:

Cov.:

AF XY:

0.00791

AC XY:

589

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00260

Gnomad4 AMR

AF:

0.00889

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.000943

Gnomad4 NFE

AF:

0.0142

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0133

Hom.:

Bravo

AF:

0.00912

TwinsUK

AF:

0.0208

AC:

ALSPAC

AF:

0.0174

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.0130

AC:

112

ExAC

AF:

0.00789

AC:

958

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PAPSS2: BP4, BS1, BS2 -

not specified

Benign:1

Feb 21, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spondyloepimetaphyseal dysplasia, PAPSS2 type

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.94

D;D

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.46

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.056

Sift

Benign

0.071

T;T

Sift4G

Benign

0.073

T;T

Polyphen

0.46

P;P

Vest4

0.52

MVP

0.55

MPC

0.50

ClinPred

0.0083

GERP RS

5.7

Varity_R

0.064

gMVP

0.54

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over