10-87659881-C-CGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001015880.2(PAPSS2):c.-77_-75dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9901 hom., cov: 0)
  • Exomes 𝑓: 0.30 (25263 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0360

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-87659881-C-CGCT is Benign according to our data. Variant chr10-87659881-C-CGCT is described in ClinVar as [Benign]. Clinvar id is 1274645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.-77_-75dup		5_prime_UTR_variant	1/13	ENST00000456849.2
PAPSS2	NM_004670.4	c.-77_-75dup		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.-77_-75dup		5_prime_UTR_variant	1/13	1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.-77_-75dup		5_prime_UTR_variant	1/12	1		P4
	ENST00000354527.2	n.122_123insAGC		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53194 AN: 150962 Hom.: 9902 Cov.: 0

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.0808

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.348

GnomAD4 exome AF: 0.305 AC: 269665 AN: 884574 Hom.: 25263 Cov.: 14 AF XY: 0.304 AC XY: 139551 AN XY: 459212

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.257

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.0713

Gnomad4 SAS exome AF: 0.222

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.337

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.352 AC: 53216 AN: 151066 Hom.: 9901 Cov.: 0 AF XY: 0.342 AC XY: 25244 AN XY: 73830

Gnomad4 AFR AF: 0.285

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.0810

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.436

Gnomad4 OTH AF: 0.345

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, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3217087; hg19: chr10-89419638;