NM_001015880.2(PAPSS2):c.883G>A (p.Gly295Ser) AND Spondyloepimetaphyseal dysplasia, PAPSS2 type

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 1, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001322588.5

Allele description [Variation Report for NM_001015880.2(PAPSS2):c.883G>A (p.Gly295Ser)]

NM_001015880.2(PAPSS2):c.883G>A (p.Gly295Ser)

Gene:

PAPSS2:3'-phosphoadenosine 5'-phosphosulfate synthase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.31

Genomic location:

Preferred name:

NM_001015880.2(PAPSS2):c.883G>A (p.Gly295Ser)

HGVS:

NC_000010.11:g.87727286G>A
NG_012150.1:g.72568G>A
NM_001015880.2:c.883G>AMANE SELECT
NM_004670.4:c.868G>A
NP_001015880.1:p.Gly295Ser
NP_004661.2:p.Gly290Ser
NC_000010.10:g.89487043G>A

Protein change:

G290S

Links:

dbSNP: rs544558219

NCBI 1000 Genomes Browser:

rs544558219

Molecular consequence:

NM_001015880.2:c.883G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004670.4:c.868G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Spondyloepimetaphyseal dysplasia, PAPSS2 type
Synonyms:: SEMD, PAKISTANI TYPE; Spondyloepimetaphyseal dysplasia, pakistani type; BRACHYOLMIA TYPE 4 WITH MILD EPIPHYSEAL AND METAPHYSEAL CHANGES
Identifiers:: MONDO: MONDO:0019666; MedGen: C2748515; Orphanet: 93282; OMIM: 612847

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001513466	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 1, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001513466

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 1, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001513466.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glycine with serine at codon 295 of the PAPSS2 protein (p.Gly295Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs544558219, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with PAPSS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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