10-87660116-C-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+108C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,152,714 control chromosomes in the GnomAD database, including 76,214 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (8790 hom., cov: 31)
  • Exomes 𝑓: 0.36 (67424 hom.)
• Consequence: PAPSS2 NM_001015880.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.10

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=-0.83).
• BP6: Variant 10-87660116-C-G is Benign according to our data. Variant chr10-87660116-C-G is described in ClinVar as [Benign]. Clinvar id is 1233069.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.27+108C>G		intron_variant		ENST00000456849.2
PAPSS2	NM_004670.4	c.27+108C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+108C>G		intron_variant		1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.27+108C>G		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50775 AN: 151854 Hom.: 8785 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.0784

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.326

GnomAD4 exome AF: 0.357 AC: 357206 AN: 1000744 Hom.: 67424 AF XY: 0.352 AC XY: 179444 AN XY: 510070

Gnomad4 AFR exome AF: 0.308

Gnomad4 AMR exome AF: 0.279

Gnomad4 ASJ exome AF: 0.331

Gnomad4 EAS exome AF: 0.0679

Gnomad4 SAS exome AF: 0.205

Gnomad4 FIN exome AF: 0.315

Gnomad4 NFE exome AF: 0.397

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.334 AC: 50802 AN: 151970 Hom.: 8790 Cov.: 31 AF XY: 0.325 AC XY: 24166 AN XY: 74310

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.0786

Gnomad4 SAS AF: 0.202

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.324

Alfa AF: 0.352 Hom.: 1201

Bravo AF: 0.333

Asia WGS AF: 0.178 AC: 620 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	-0.83
Cadd	Benign	0.14
Dann	Benign	0.69

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: rs2255682; hg19: chr10-89419873;