10-87660214-C-T

Variant names:

• chr10-87660214-C-T
• rs2255684
• NM_001015880.2:c.27+206C>T

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+206C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 620,786 control chromosomes in the GnomAD database, including 35,352 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8450 hom., cov: 32)
  • Exomes 𝑓: 0.33 (26902 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.526
• Publications: 6 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 10-87660214-C-T is Benign according to our data. Variant chr10-87660214-C-T is described in ClinVar as [Benign]. Clinvar id is 1239633.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+206C>T		intron_variant	Intron 1 of 12	ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+206C>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+206C>T		intron_variant	Intron 1 of 12	1	NM_001015880.2	ENSP00000406157.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49777 AN: 151862 Hom.: 8444 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.0792

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.319

GnomAD4 exome AF: 0.326 AC: 152616 AN: 468806 Hom.: 26902 AF XY: 0.321 AC XY: 79462 AN XY: 247770

African (AFR) AF: 0.306 AC: 3935 AN: 12840

American (AMR) AF: 0.282 AC: 5784 AN: 20530

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 4433 AN: 14030

East Asian (EAS) AF: 0.0725 AC: 2250 AN: 31032

South Asian (SAS) AF: 0.204 AC: 9539 AN: 46850

European-Finnish (FIN) AF: 0.297 AC: 9071 AN: 30506

Middle Eastern (MID) AF: 0.292 AC: 591 AN: 2022

European-Non Finnish (NFE) AF: 0.381 AC: 108351 AN: 284328

Other (OTH) AF: 0.325 AC: 8662 AN: 26668

GnomAD4 genome AF: 0.328 AC: 49809 AN: 151980 Hom.: 8450 Cov.: 32 AF XY: 0.318 AC XY: 23651 AN XY: 74304

African (AFR) AF: 0.309 AC: 12788 AN: 41452

American (AMR) AF: 0.300 AC: 4587 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.0794 AC: 407 AN: 5126

South Asian (SAS) AF: 0.203 AC: 980 AN: 4820

European-Finnish (FIN) AF: 0.286 AC: 3024 AN: 10590

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.382 AC: 25945 AN: 67928

Other (OTH) AF: 0.317 AC: 668 AN: 2110

Alfa AF: 0.359 Hom.: 17975

Bravo AF: 0.328

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Apr 09, 2019

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	-0.74
CADD	Benign	11
DANN	Benign	0.88
PhyloP100		0.53
PromoterAI		-0.040	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: rs2255684; hg19: chr10-89419971;