Genetic Variant PAPSS2:c.-80_-75delTGCTGC (chr10-87659881-CGCTGCT-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001015880.2(PAPSS2):c.-80_-75delTGCTGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000981 in 1,037,656 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

PAPSS2
NM_001015880.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.779

Publications

2 publications found

Variant links:

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]

PAPSS2 Gene-Disease associations (from GenCC):

spondyloepimetaphyseal dysplasia, PAPSS2 type
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet, Ambry Genetics
autosomal recessive brachyolmia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

PAPSS2 links:

ENSG00000196566 (HGNC:):

ENSG00000196566 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00221 (334/151168) while in subpopulation AFR AF = 0.00672 (277/41232). AF 95% confidence interval is 0.00607. There are 0 homozygotes in GnomAd4. There are 149 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2 link	c.-80_-75delTGCTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1	O95340-2
PAPSS2	NM_004670.4 link	c.-80_-75delTGCTGC		5_prime_UTR_variant	Exon 1 of 12		NP_004661.2	O95340-1Q5TB52

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAPSS2	ENST00000456849.2 link	c.-80_-75delTGCTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1		O95340-2

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

334

AN:

151064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00674

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000527

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000956

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000680

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000772

AC:

684

AN:

886488

Hom.:

AF XY:

0.000663

AC XY:

305

AN XY:

460138

show subpopulations

African (AFR)

AF:

0.00702

AC:

154

AN:

21940

American (AMR)

AF:

0.000837

AC:

AN:

39414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21948

East Asian (EAS)

AF:

0.00

AC:

AN:

34838

South Asian (SAS)

AF:

0.000139

AC:

AN:

72020

European-Finnish (FIN)

AF:

0.0000642

AC:

AN:

46758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4434

European-Non Finnish (NFE)

AF:

0.000738

AC:

446

AN:

604056

Other (OTH)

AF:

0.000925

AC:

AN:

41080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

113

141

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00221

AC:

334

AN:

151168

Hom.:

Cov.:

AF XY:

0.00202

AC XY:

149

AN XY:

73876

show subpopulations

African (AFR)

AF:

0.00672

AC:

277

AN:

41232

American (AMR)

AF:

0.000526

AC:

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.000208

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0000956

AC:

AN:

10464

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000680

AC:

AN:

67604

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

286

Bravo

AF:

0.00238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.78

Mutation Taster

=299/1

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

10-87659881-CGCTGCT-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over