10-87660300-C-T

Variant names:

• chr10-87660300-C-T
• rs2302402
• NM_001015880.2:c.27+292C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001015880.2(PAPSS2):​c.27+292C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 573,302 control chromosomes in the GnomAD database, including 19,258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6182 hom., cov: 31)
  • Exomes 𝑓: 0.24 (13076 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.49
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 10-87660300-C-T is Benign according to our data. Variant chr10-87660300-C-T is described in ClinVar as [Benign]. Clinvar id is 1220957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.389 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+292C>T		intron_variant	Intron 1 of 12	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+292C>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+292C>T		intron_variant	Intron 1 of 12	1	NM_001015880.2	ENSP00000406157.1

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40709 AN: 151902 Hom.: 6165 Cov.: 31

Gnomad AFR AF: 0.393

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.236 AC: 99543 AN: 421282 Hom.: 13076 AF XY: 0.241 AC XY: 53335 AN XY: 221586

African (AFR) AF: 0.390 AC: 4554 AN: 11682

American (AMR) AF: 0.214 AC: 3744 AN: 17508

Ashkenazi Jewish (ASJ) AF: 0.245 AC: 3153 AN: 12860

East Asian (EAS) AF: 0.377 AC: 10941 AN: 29042

South Asian (SAS) AF: 0.331 AC: 14148 AN: 42732

European-Finnish (FIN) AF: 0.304 AC: 8434 AN: 27724

Middle Eastern (MID) AF: 0.271 AC: 498 AN: 1836

European-Non Finnish (NFE) AF: 0.190 AC: 48164 AN: 253446

Other (OTH) AF: 0.242 AC: 5907 AN: 24452

GnomAD4 genome AF: 0.268 AC: 40770 AN: 152020 Hom.: 6182 Cov.: 31 AF XY: 0.274 AC XY: 20375 AN XY: 74308

African (AFR) AF: 0.394 AC: 16323 AN: 41444

American (AMR) AF: 0.226 AC: 3451 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.341 AC: 1755 AN: 5150

South Asian (SAS) AF: 0.336 AC: 1615 AN: 4804

European-Finnish (FIN) AF: 0.306 AC: 3237 AN: 10566

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12689 AN: 67980

Other (OTH) AF: 0.265 AC: 558 AN: 2108

Alfa AF: 0.236 Hom.: 592

Bravo AF: 0.265

Asia WGS AF: 0.355 AC: 1236 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.96
PhyloP100		-1.5
PromoterAI		0.0095	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2302402; hg19: chr10-89420057;