10-87659881-CGCTGCTGCTGCT-CGCTGCTGCTGCTGCTGCTGCT

Variant names:

• chr10-87659881-C-CGCTGCTGCT
• rs3217087
• NM_001015880.2:c.-83_-75dupTGCTGCTGC

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001015880.2(PAPSS2):​c.-83_-75dupTGCTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.042 (436 hom., cov: 0)
  • Exomes 𝑓: 0.0046 (98 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360
• 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: 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 -10 ACMG points.

• BP6: Variant 10-87659881-C-CGCTGCTGCT is Benign according to our data. Variant chr10-87659881-C-CGCTGCTGCT is described in ClinVar as Benign. ClinVar VariationId is 1274995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 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.-83_-75dupTGCTGCTGC		5_prime_UTR	Exon 1 of 13	NP_001015880.1	O95340-2
	PAPSS2	NM_004670.4		c.-83_-75dupTGCTGCTGC		5_prime_UTR	Exon 1 of 12	NP_004661.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PAPSS2	ENST00000456849.2	TSL:1 MANE Select	c.-83_-75dupTGCTGCTGC		5_prime_UTR	Exon 1 of 13	ENSP00000406157.1	O95340-2
	PAPSS2	ENST00000361175.8	TSL:1	c.-83_-75dupTGCTGCTGC		5_prime_UTR	Exon 1 of 12	ENSP00000354436.4	O95340-1
	PAPSS2	ENST00000904622.1		c.-83_-75dupTGCTGCTGC		5_prime_UTR	Exon 1 of 13	ENSP00000574681.1

Frequencies

GnomAD3 genomes AF: 0.0424 AC: 6408 AN: 151036 Hom.: 436 Cov.: 0

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.0298

Gnomad AMR AF: 0.0165

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00125

Gnomad FIN AF: 0.0000956

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000887

Gnomad OTH AF: 0.0272

GnomAD4 exome AF: 0.00463 AC: 4106 AN: 886490 Hom.: 98 Cov.: 14 AF XY: 0.00392 AC XY: 1805 AN XY: 460136

African (AFR) AF: 0.135 AC: 2957 AN: 21910

American (AMR) AF: 0.00807 AC: 318 AN: 39404

Ashkenazi Jewish (ASJ) AF: 0.000228 AC: 5 AN: 21948

East Asian (EAS) AF: 0.0000287 AC: 1 AN: 34844

South Asian (SAS) AF: 0.000583 AC: 42 AN: 72014

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46760

Middle Eastern (MID) AF: 0.00812 AC: 36 AN: 4436

European-Non Finnish (NFE) AF: 0.000459 AC: 277 AN: 604094

Other (OTH) AF: 0.0114 AC: 470 AN: 41080

GnomAD4 genome AF: 0.0425 AC: 6416 AN: 151140 Hom.: 436 Cov.: 0 AF XY: 0.0411 AC XY: 3034 AN XY: 73864

African (AFR) AF: 0.146 AC: 6012 AN: 41208

American (AMR) AF: 0.0164 AC: 250 AN: 15208

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4800

European-Finnish (FIN) AF: 0.0000956 AC: 1 AN: 10464

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000888 AC: 60 AN: 67602

Other (OTH) AF: 0.0269 AC: 56 AN: 2080

Alfa AF: 0.00 Hom.: 286

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
PhyloP100		0.036
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3217087; hg19: chr10-89419638;