NM_001282717.2(STAG3):c.1573+5G>A AND Premature ovarian failure 8

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 20, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000494704.3

Allele description [Variation Report for NM_001282717.2(STAG3):c.1573+5G>A]

NM_001282717.2(STAG3):c.1573+5G>A

Gene:

STAG3:STAG3 cohesin complex component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q22.1

Genomic location:

Preferred name:

NM_001282717.2(STAG3):c.1573+5G>A

HGVS:

NC_000007.14:g.100199372G>A
NG_034114.1:g.26649G>A
NM_001282716.1:c.1573+5G>A
NM_001282717.2:c.1573+5G>AMANE SELECT
NM_001282718.2:c.1399+5G>A
NM_001375438.1:c.1573+5G>A
NM_012447.4:c.1573+5G>A
NC_000007.13:g.99796995G>A
NM_012447.2:c.1573+5G>A

Nucleotide change:

IVS15, G-A, +5 (rs376787666)

Links:

OMIM: 608489.0003; dbSNP: rs376787666

NCBI 1000 Genomes Browser:

rs376787666

Molecular consequence:

NM_001282716.1:c.1573+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282717.2:c.1573+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001282718.2:c.1399+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001375438.1:c.1573+5G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_012447.4:c.1573+5G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Premature ovarian failure 8 (POF8)
Identifiers:: MONDO: MONDO:0014321; MedGen: C3810367; OMIM: 615723

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000581391	Institute of Reproductive and Stem Cell Engineering, Central South University	no assertion criteria provided	Pathogenic (Apr 10, 2017)	germline, not applicable	research	PubMed (1) [See all records that cite this PMID]
SCV002039144	OMIM	no assertion criteria provided	Pathogenic (Dec 20, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000581391

Institute of Reproductive and Stem Cell Engineering, Central South University

no assertion criteria provided

Pathogenic
(Apr 10, 2017)

germline, not applicable

research

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

SCV002039144

OMIM

no assertion criteria provided

Pathogenic
(Dec 20, 2021)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	not applicable	not applicable	not provided	not provided	not provided	not provided	not provided	research
Chinese Han population	germline	no	not provided	not provided	not provided	not provided	not provided	research
Chinese Han population	germline	yes	2	1	not provided	not provided	not provided	research

Citations

PubMed

Whole-exome sequencing identifies a homozygous donor splice-site mutation in STAG3 that causes primary ovarian insufficiency.

He WB, Banerjee S, Meng LL, Du J, Gong F, Huang H, Zhang XX, Wang YY, Lu GX, Lin G, Tan YQ.

Clin Genet. 2018 Feb;93(2):340-344. doi: 10.1111/cge.13034. Epub 2017 Aug 17.

PubMed [citation]

PMID:: 28393351

Details of each submission

From Institute of Reproductive and Stem Cell Engineering, Central South University, SCV000581391.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)
2	Chinese Han population	2	not provided	not provided	research	PubMed (1)
3	Chinese Han population	not provided	not provided	not provided	research	PubMed (1)

Description

not provided

RT-PCR revealed that the mutation causes loss of wild type donor splice site which leads to aberrant splicing of STAG3 mRNA and consecutive formation of STAG3 alternative transcript (p.Leu490Thrfs*10) .

Description

Whole exome and Sanger sequencing identified a homozygous donor splice site mutation (NM_012447.2: c.1573+5G>A) in the STAG3 gene. RT-PCR revealed that the mutation causes loss of wild type donor splice site which leads to aberrant splicing of STAG3 mRNA and consecutive formation of STAG3 alternative transcript (p.Leu490Thrfs*10) . This is the first report of splice-site mutation of STAG3 gene causes POI in two Han Chinese patients.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not applicable	not applicable	not provided	Blood	not provided		not provided	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		2	not provided	1	not provided
3	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From OMIM, SCV002039144.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 Han Chinese sisters with premature ovarian failure (POF8; 615723), He et al. (2018) identified homozygosity for a c.1573+5G-A transition (c.1573+5G-A, NM_012447.2) in intron 15 of the STAG3 gene. Their unaffected parents and brother were heterozygous for the mutation, which was not found in the 1000 Genomes Project or ExAC databases, but was present in the GO-ESP database at low minor allele frequency (0.00008). RT-PCR of patient mRNA showed a truncated fragment resulting from skipping of exon 15 with out-of-frame fusion of exons 14 and 16, causing a frameshift resulting in a premature termination codon (Leu490ThrfsTer10). Both sisters presented with primary amenorrhea, small and undeveloped breasts, and streak gonads with elevated gonadotropins.

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

Last Updated: Jun 23, 2024

ClinVar

Relating variation to medicine