10-87709326-CATAT-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001015880.2(PAPSS2):c.145+29_145+32del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,153,434 control chromosomes in the GnomAD database, including 99,616 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20090 hom., cov: 0)
  • Exomes 𝑓: 0.43 (79526 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0260

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 10-87709326-CATAT-C is Benign according to our data. Variant chr10-87709326-CATAT-C is described in ClinVar as [Benign]. Clinvar id is 1164974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87709326-CATAT-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.145+29_145+32del		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.145+29_145+32del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.145+29_145+32del		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.145+29_145+32del		intron_variant		1		P4
PAPSS2	ENST00000465996.5	n.167+29_167+32del		intron_variant, non_coding_transcript_variant		2
PAPSS2	ENST00000482258.1	n.188+29_188+32del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.507 AC: 75876 AN: 149512 Hom.: 20047 Cov.: 0

Gnomad AFR AF: 0.608

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.529

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.430 AC: 432085 AN: 1003814 Hom.: 79526 AF XY: 0.433 AC XY: 223589 AN XY: 516594

Gnomad4 AFR exome AF: 0.555

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.701

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.472

Gnomad4 NFE exome AF: 0.391

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.508 AC: 75977 AN: 149620 Hom.: 20090 Cov.: 0 AF XY: 0.516 AC XY: 37650 AN XY: 72968

Gnomad4 AFR AF: 0.608

Gnomad4 AMR AF: 0.529

Gnomad4 ASJ AF: 0.342

Gnomad4 EAS AF: 0.788

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.418

Gnomad4 OTH AF: 0.484

Bravo AF: 0.517

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spondyloepimetaphyseal dysplasia, PAPSS2 type Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs72025574; hg19: chr10-89469083;