10-87660214-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.27+206C>T		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.27+206C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+206C>T		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.27+206C>T		intron_variant		1		P4

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

Gnomad4 AFR exome AF: 0.306

Gnomad4 AMR exome AF: 0.282

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.0725

Gnomad4 SAS exome AF: 0.204

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.381

Gnomad4 OTH exome AF: 0.325

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

Gnomad4 AFR AF: 0.309

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.0794

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.317

Alfa AF: 0.354 Hom.: 4508

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

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 09, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	11
Dann	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs2255684; hg19: chr10-89419971;