10-87659881-CGCTGCTGCTGCT-C

Variant names:

• chr10-87659881-CGCTGCTGCTGCT-C
• rs3217087
• NM_001015880.2:c.-86_-75delTGCTGCTGCTGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001015880.2(PAPSS2):​c.-86_-75delTGCTGCTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 886,570 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000024 (0 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779
• Publications: 0 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

ENSG00000196566 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.-86_-75delTGCTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.-86_-75delTGCTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 12		NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2	c.-86_-75delTGCTGCTGCTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000237 AC: 21 AN: 886570 Hom.: 0 AF XY: 0.0000239 AC XY: 11 AN XY: 460176

African (AFR) AF: 0.00 AC: 0 AN: 21942

American (AMR) AF: 0.00 AC: 0 AN: 39416

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21948

East Asian (EAS) AF: 0.00 AC: 0 AN: 34844

South Asian (SAS) AF: 0.00 AC: 0 AN: 72020

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4436

European-Non Finnish (NFE) AF: 0.0000348 AC: 21 AN: 604120

Other (OTH) AF: 0.00 AC: 0 AN: 41084

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.78

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;