rs2255683

Variant names:

• chr10-87660153-A-G
• rs2255683
• NM_001015880.2:c.27+145A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001015880.2(PAPSS2):​c.27+145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 809,262 control chromosomes in the GnomAD database, including 139,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30808 hom., cov: 31)
  • Exomes 𝑓: 0.57 (108608 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290
• Publications: 4 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet
• autosomal recessive brachyolmia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000196566 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-87660153-A-G is Benign according to our data. Variant chr10-87660153-A-G is described in ClinVar as Benign. ClinVar VariationId is 1244163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS2	NM_001015880.2	MANE Select	c.27+145A>G		intron	N/A	NP_001015880.1	O95340-2
	PAPSS2	NM_004670.4		c.27+145A>G		intron	N/A	NP_004661.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS2	ENST00000456849.2	TSL:1 MANE Select	c.27+145A>G		intron	N/A	ENSP00000406157.1	O95340-2
	PAPSS2	ENST00000361175.8	TSL:1	c.27+145A>G		intron	N/A	ENSP00000354436.4	O95340-1
	PAPSS2	ENST00000904622.1		c.27+145A>G		intron	N/A	ENSP00000574681.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95230 AN: 151840 Hom.: 30763 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.570 AC: 374495 AN: 657302 Hom.: 108608 AF XY: 0.568 AC XY: 197421 AN XY: 347546

African (AFR) AF: 0.795 AC: 13865 AN: 17446

American (AMR) AF: 0.495 AC: 16613 AN: 33544

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 11616 AN: 19778

East Asian (EAS) AF: 0.447 AC: 14400 AN: 32250

South Asian (SAS) AF: 0.535 AC: 33950 AN: 63438

European-Finnish (FIN) AF: 0.598 AC: 25092 AN: 41984

Middle Eastern (MID) AF: 0.573 AC: 1528 AN: 2666

European-Non Finnish (NFE) AF: 0.577 AC: 238079 AN: 412780

Other (OTH) AF: 0.579 AC: 19352 AN: 33416

GnomAD4 genome AF: 0.627 AC: 95329 AN: 151960 Hom.: 30808 Cov.: 31 AF XY: 0.623 AC XY: 46259 AN XY: 74258

African (AFR) AF: 0.799 AC: 33184 AN: 41506

American (AMR) AF: 0.535 AC: 8175 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.584 AC: 2021 AN: 3462

East Asian (EAS) AF: 0.414 AC: 2118 AN: 5114

South Asian (SAS) AF: 0.542 AC: 2614 AN: 4820

European-Finnish (FIN) AF: 0.595 AC: 6294 AN: 10580

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.575 AC: 39012 AN: 67894

Other (OTH) AF: 0.606 AC: 1277 AN: 2108

Alfa AF: 0.603 Hom.: 3528

Bravo AF: 0.628

Asia WGS AF: 0.539 AC: 1879 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.9
DANN	Benign	0.61
PhyloP100		-0.029
PromoterAI		-0.010	Neutral
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: rs2255683; hg19: chr10-89419910; COSMIC: COSV63265272; COSMIC: COSV63265272;