10-87683553-T-C

Variant names:

• chr10-87683553-T-C
• rs10887741
• NM_001015880.2:c.27+23545T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001015880.2(PAPSS2):​c.27+23545T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,110 control chromosomes in the GnomAD database, including 8,771 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 0.33 (8771 hom., cov: 32)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 16 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

ENSG00000225913 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+23545T>C		intron_variant	Intron 1 of 12	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+23545T>C		intron_variant	Intron 1 of 11		NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+23545T>C		intron_variant	Intron 1 of 12	1	NM_001015880.2	ENSP00000406157.1

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49691 AN: 151992 Hom.: 8774 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.444

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.327 AC: 49703 AN: 152110 Hom.: 8771 Cov.: 32 AF XY: 0.328 AC XY: 24400 AN XY: 74354

African (AFR) AF: 0.176 AC: 7307 AN: 41528

American (AMR) AF: 0.354 AC: 5408 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.314 AC: 1087 AN: 3466

East Asian (EAS) AF: 0.445 AC: 2301 AN: 5176

South Asian (SAS) AF: 0.349 AC: 1685 AN: 4822

European-Finnish (FIN) AF: 0.381 AC: 4024 AN: 10564

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26663 AN: 67972

Other (OTH) AF: 0.326 AC: 688 AN: 2108

Alfa AF: 0.367 Hom.: 30951

Bravo AF: 0.321

Asia WGS AF: 0.345 AC: 1199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.25
DANN	Benign	0.41
PhyloP100		-0.96
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: rs10887741; hg19: chr10-89443310;