10-87709326-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001015880.2(PAPSS2):c.145+31_145+32del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 1,092,236 control chromosomes in the GnomAD database, including 10 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0049 (9 hom., cov: 0)
  • Exomes 𝑓: 0.037 (1 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 10-87709326-CAT-C is Benign according to our data. Variant chr10-87709326-CAT-C is described in ClinVar as [Benign]. Clinvar id is 1599026.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-87709326-CAT-C is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00492 (736/149486) while in subpopulation AFR AF= 0.015 (614/40840). AF 95% confidence interval is 0.0141. There are 9 homozygotes in gnomad4. There are 331 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.145+31_145+32del		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.145+31_145+32del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.145+31_145+32del		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.145+31_145+32del		intron_variant		1		P4
PAPSS2	ENST00000465996.5	n.167+31_167+32del		intron_variant, non_coding_transcript_variant		2
PAPSS2	ENST00000482258.1	n.188+31_188+32del		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00492 AC: 735 AN: 149378 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.0151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00187

Gnomad ASJ AF: 0.000291

Gnomad EAS AF: 0.000392

Gnomad SAS AF: 0.000631

Gnomad FIN AF: 0.000993

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.00294

GnomAD4 exome AF: 0.0366 AC: 34489 AN: 942750 Hom.: 1 AF XY: 0.0370 AC XY: 17907 AN XY: 483806

Gnomad4 AFR exome AF: 0.0328

Gnomad4 AMR exome AF: 0.0245

Gnomad4 ASJ exome AF: 0.0635

Gnomad4 EAS exome AF: 0.0100

Gnomad4 SAS exome AF: 0.0180

Gnomad4 FIN exome AF: 0.0333

Gnomad4 NFE exome AF: 0.0400

Gnomad4 OTH exome AF: 0.0382

GnomAD4 genome AF: 0.00492 AC: 736 AN: 149486 Hom.: 9 Cov.: 0 AF XY: 0.00454 AC XY: 331 AN XY: 72926

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.00187

Gnomad4 ASJ AF: 0.000291

Gnomad4 EAS AF: 0.000393

Gnomad4 SAS AF: 0.000632

Gnomad4 FIN AF: 0.000993

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.00291

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Spondyloepimetaphyseal dysplasia, PAPSS2 type Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

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;