Genetic Variant NM_001015880.2:c.-77_-75dupTGC (chr10-87659881-C-CGCT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001015880.2(PAPSS2):c.-77_-75dupTGC 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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0360

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: Benign. The variant received -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 rank	MANE	Protein	UniProt
PAPSS2	NM_001015880.2 link	c.-77_-75dupTGC		5_prime_UTR_variant	Exon 1 of 13	ENST00000456849.2	NP_001015880.1	O95340-2
PAPSS2	NM_004670.4 link	c.-77_-75dupTGC		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.-77_-75dupTGC		5_prime_UTR_variant	Exon 1 of 13	1	NM_001015880.2	ENSP00000406157.1		O95340-2

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53194

AN:

150962

Hom.:

9902

Cov.:

show subpopulations

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.:

AF XY:

0.304

AC XY:

139551

AN XY:

459212

show subpopulations

African (AFR)

AF:

0.239

AC:

5234

AN:

21902

American (AMR)

AF:

0.257

AC:

10111

AN:

39362

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

6379

AN:

21918

East Asian (EAS)

AF:

0.0713

AC:

2484

AN:

34834

South Asian (SAS)

AF:

0.222

AC:

15993

AN:

71980

European-Finnish (FIN)

AF:

0.288

AC:

13441

AN:

46688

Middle Eastern (MID)

AF:

0.244

AC:

1079

AN:

4426

European-Non Finnish (NFE)

AF:

0.337

AC:

202828

AN:

602430

Other (OTH)

AF:

0.295

AC:

12116

AN:

41034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

8897

17794

26690

35587

44484

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.352

AC:

53216

AN:

151066

Hom.:

9901

Cov.:

AF XY:

0.342

AC XY:

25244

AN XY:

73830

show subpopulations

African (AFR)

AF:

0.285

AC:

11722

AN:

41196

American (AMR)

AF:

0.314

AC:

4781

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1141

AN:

3452

East Asian (EAS)

AF:

0.0810

AC:

415

AN:

5122

South Asian (SAS)

AF:

0.249

AC:

1194

AN:

4798

European-Finnish (FIN)

AF:

0.325

AC:

3398

AN:

10450

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.436

AC:

29462

AN:

67562

Other (OTH)

AF:

0.345

AC:

716

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1637

3274

4912

6549

8186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.156

Hom.:

286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 27, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.036

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

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NM_001015880.2:c.-77_-75dupTGC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over