rs1321934

Positions:

• chr10-87735607-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001015880.2(PAPSS2):​c.1087-5628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,940 control chromosomes in the GnomAD database, including 13,661 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13661 hom., cov: 31)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.1087-5628G>A		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.1072-5628G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.1087-5628G>A		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.1072-5628G>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62570 AN: 151822 Hom.: 13642 Cov.: 31

Gnomad AFR AF: 0.560

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.382

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.407

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.412 AC: 62634 AN: 151940 Hom.: 13661 Cov.: 31 AF XY: 0.413 AC XY: 30692 AN XY: 74254

Gnomad4 AFR AF: 0.560

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.343

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.383

Gnomad4 FIN AF: 0.382

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.414

Alfa AF: 0.352 Hom.: 19750

Bravo AF: 0.415

Asia WGS AF: 0.444 AC: 1542 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.32

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: rs1321934; hg19: chr10-89495364;