10-87660153-A-G

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+145A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 809,262 control chromosomes in the GnomAD database, including 139,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.63 (30808 hom., cov: 31)
  • Exomes 𝑓: 0.57 (108608 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

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=-0.87).
• BP6: Variant 10-87660153-A-G is Benign according to our data. Variant chr10-87660153-A-G is described in ClinVar as [Benign]. Clinvar id is 1244163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.27+145A>G		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.27+145A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+145A>G		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.27+145A>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95230 AN: 151840 Hom.: 30763 Cov.: 31

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.584

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.543

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.575

Gnomad OTH AF: 0.609

GnomAD4 exome AF: 0.570 AC: 374495 AN: 657302 Hom.: 108608 AF XY: 0.568 AC XY: 197421 AN XY: 347546

Gnomad4 AFR exome AF: 0.795

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.587

Gnomad4 EAS exome AF: 0.447

Gnomad4 SAS exome AF: 0.535

Gnomad4 FIN exome AF: 0.598

Gnomad4 NFE exome AF: 0.577

Gnomad4 OTH exome AF: 0.579

GnomAD4 genome AF: 0.627 AC: 95329 AN: 151960 Hom.: 30808 Cov.: 31 AF XY: 0.623 AC XY: 46259 AN XY: 74258

Gnomad4 AFR AF: 0.799

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.584

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.595

Gnomad4 NFE AF: 0.575

Gnomad4 OTH AF: 0.606

Alfa AF: 0.603 Hom.: 3528

Bravo AF: 0.628

Asia WGS AF: 0.539 AC: 1879 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

Jul 27, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	6.9
Dann	Benign	0.61

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: rs2255683; hg19: chr10-89419910; COSMIC: COSV63265272; COSMIC: COSV63265272;