rs1321934

Variant names:

• chr10-87735607-G-A
• rs1321934
• NM_001015880.2:c.1087-5628G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.

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.1087-5628G>A		intron	N/A	NP_001015880.1
	PAPSS2	NM_004670.4		c.1072-5628G>A		intron	N/A	NP_004661.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS2	ENST00000456849.2	TSL:1 MANE Select	c.1087-5628G>A		intron	N/A	ENSP00000406157.1
	PAPSS2	ENST00000361175.8	TSL:1	c.1072-5628G>A		intron	N/A	ENSP00000354436.4

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

African (AFR) AF: 0.560 AC: 23208 AN: 41420

American (AMR) AF: 0.338 AC: 5159 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1191 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2530 AN: 5160

South Asian (SAS) AF: 0.383 AC: 1846 AN: 4818

European-Finnish (FIN) AF: 0.382 AC: 4027 AN: 10540

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23374 AN: 67950

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.361 Hom.: 43883

Bravo AF: 0.415

Asia WGS AF: 0.444 AC: 1542 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.32
PhyloP100		-0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1321934; hg19: chr10-89495364;