10-87660300-C-T

Position:

• chr10-87660300-C-T

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	Protein	UniProt
PAPSS2	NM_001015880.2	c.27+292C>T		intron_variant		ENST00000456849.2	NP_001015880.1
PAPSS2	NM_004670.4	c.27+292C>T		intron_variant			NP_004661.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2	c.27+292C>T		intron_variant		1	NM_001015880.2	ENSP00000406157.1
PAPSS2	ENST00000361175.8	c.27+292C>T		intron_variant		1		ENSP00000354436.4

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

Gnomad4 AFR exome AF: 0.390

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.377

Gnomad4 SAS exome AF: 0.331

Gnomad4 FIN exome AF: 0.304

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.242

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

Gnomad4 AFR AF: 0.394

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.265

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	1.8
DANN	Benign	0.96

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

Publications

LitVar

Other links and lift over

dbSNP: rs2302402; hg19: chr10-89420057;