10-87660116-C-T

Variant names:

• chr10-87660116-C-T
• rs2255682
• NM_001015880.2:c.27+108C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001015880.2(PAPSS2):​c.27+108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000997 in 1,002,710 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000010 (0 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+108C>T		intron_variant	Intron 1 of 12	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+108C>T		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+108C>T		intron_variant	Intron 1 of 12	1	NM_001015880.2	ENSP00000406157.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 9.97e-7 AC: 1 AN: 1002710 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 511028

African (AFR) AF: 0.00 AC: 0 AN: 24250

American (AMR) AF: 0.00 AC: 0 AN: 35570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22664

East Asian (EAS) AF: 0.00 AC: 0 AN: 34372

South Asian (SAS) AF: 0.00 AC: 0 AN: 71926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47718

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3812

European-Non Finnish (NFE) AF: 0.00000139 AC: 1 AN: 717428

Other (OTH) AF: 0.00 AC: 0 AN: 44970

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.20
DANN	Benign	0.90
PhyloP100		-2.1
PromoterAI		0.0014	Neutral

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: rs2255682; hg19: chr10-89419873;