10-87659881-C-CGCTGCTGCTGCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001015880.2(PAPSS2):c.-86_-75dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (28 hom., cov: 0)
  • Exomes 𝑓: 0.0058 (18 hom.)
• Consequence: PAPSS2 NM_001015880.2 5_prime_UTR
• Clinical Significance: Likely 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-CGCTGCTGCTGCT is Benign according to our data. Variant chr10-87659881-C-CGCTGCTGCTGCT is described in ClinVar as [Likely_benign]. Clinvar id is 1326444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0156 (2353/151154) while in subpopulation AFR AF= 0.0403 (1663/41224). AF 95% confidence interval is 0.0387. There are 28 homozygotes in gnomad4. There are 1108 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAPSS2	NM_001015880.2	c.-86_-75dup		5_prime_UTR_variant	1/13	ENST00000456849.2
PAPSS2	NM_004670.4	c.-86_-75dup		5_prime_UTR_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAPSS2	ENST00000456849.2	c.-86_-75dup		5_prime_UTR_variant	1/13	1	NM_001015880.2	A1
PAPSS2	ENST00000361175.8	c.-86_-75dup		5_prime_UTR_variant	1/12	1		P4
	ENST00000354527.2	n.122_123insAGCAGCAGCAGC		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2349 AN: 151050 Hom.: 28 Cov.: 0

Gnomad AFR AF: 0.0403

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00839

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00333

Gnomad FIN AF: 0.00325

Gnomad MID AF: 0.0318

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.0170

GnomAD4 exome AF: 0.00576 AC: 5104 AN: 886518 Hom.: 18 Cov.: 14 AF XY: 0.00569 AC XY: 2617 AN XY: 460142

Gnomad4 AFR exome AF: 0.0362

Gnomad4 AMR exome AF: 0.00799

Gnomad4 ASJ exome AF: 0.00820

Gnomad4 EAS exome AF: 0.000115

Gnomad4 SAS exome AF: 0.00383

Gnomad4 FIN exome AF: 0.00248

Gnomad4 NFE exome AF: 0.00487

Gnomad4 OTH exome AF: 0.00986

GnomAD4 genome AF: 0.0156 AC: 2353 AN: 151154 Hom.: 28 Cov.: 0 AF XY: 0.0150 AC XY: 1108 AN XY: 73870

Gnomad4 AFR AF: 0.0403

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.00839

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00292

Gnomad4 FIN AF: 0.00325

Gnomad4 NFE AF: 0.00572

Gnomad4 OTH AF: 0.0168

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

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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;