rs2056726

Variant names:

• chr7-100182660-G-A
• rs2056726
• NM_001282717.2:c.220-63G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282717.2(STAG3):​c.220-63G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,573,942 control chromosomes in the GnomAD database, including 35,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2710 hom., cov: 32)
  • Exomes 𝑓: 0.21 (32822 hom.)
• Consequence: STAG3 NM_001282717.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.534
• Publications: 11 publications found

Genes affected

STAG3 (HGNC:11356): (STAG3 cohesin complex component) The protein encoded by this gene is expressed in the nucleus and is a subunit of the cohesin complex which regulates the cohesion of sister chromatids during cell division. A mutation in this gene is associated with premature ovarian failure. Alternate splicing results in multiple transcript variants encoding distinct isoforms. This gene has multiple pseudogenes. [provided by RefSeq, Apr 2014]

STAG3 Gene-Disease associations (from GenCC):

• premature ovarian failure 8

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• spermatogenic failure 61

  Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 7-100182660-G-A is Benign according to our data. Variant chr7-100182660-G-A is described in ClinVar as Benign. ClinVar VariationId is 1280663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282717.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	NM_001282717.2	MANE Select	c.220-63G>A		intron	N/A	NP_001269646.1	D6W5U7
	STAG3	NM_001375438.1		c.220-63G>A		intron	N/A	NP_001362367.1	D6W5U7
	STAG3	NM_001282716.1		c.220-63G>A		intron	N/A	NP_001269645.1	Q9UJ98-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAG3	ENST00000615138.5	TSL:1 MANE Select	c.220-63G>A		intron	N/A	ENSP00000477973.1	D6W5U7
	STAG3	ENST00000317296.9	TSL:1	c.220-63G>A		intron	N/A	ENSP00000319318.5	Q9UJ98-1
	STAG3	ENST00000426455.5	TSL:1	c.220-63G>A		intron	N/A	ENSP00000400359.1	Q9UJ98-1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25357 AN: 151996 Hom.: 2704 Cov.: 32

Gnomad AFR AF: 0.0566

Gnomad AMI AF: 0.307

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0594

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.193

GnomAD4 exome AF: 0.208 AC: 295659 AN: 1421828 Hom.: 32822 AF XY: 0.209 AC XY: 148430 AN XY: 709558

African (AFR) AF: 0.0513 AC: 1654 AN: 32234

American (AMR) AF: 0.110 AC: 4791 AN: 43442

Ashkenazi Jewish (ASJ) AF: 0.351 AC: 9002 AN: 25642

East Asian (EAS) AF: 0.0594 AC: 2347 AN: 39480

South Asian (SAS) AF: 0.168 AC: 14213 AN: 84438

European-Finnish (FIN) AF: 0.230 AC: 12219 AN: 53122

Middle Eastern (MID) AF: 0.368 AC: 2084 AN: 5664

European-Non Finnish (NFE) AF: 0.219 AC: 236703 AN: 1078940

Other (OTH) AF: 0.215 AC: 12646 AN: 58866

GnomAD4 genome AF: 0.167 AC: 25362 AN: 152114 Hom.: 2710 Cov.: 32 AF XY: 0.167 AC XY: 12381 AN XY: 74356

African (AFR) AF: 0.0566 AC: 2349 AN: 41514

American (AMR) AF: 0.140 AC: 2144 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1271 AN: 3466

East Asian (EAS) AF: 0.0595 AC: 309 AN: 5194

South Asian (SAS) AF: 0.156 AC: 753 AN: 4816

European-Finnish (FIN) AF: 0.234 AC: 2472 AN: 10554

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15286 AN: 67986

Other (OTH) AF: 0.191 AC: 403 AN: 2114

Alfa AF: 0.187 Hom.: 369

Bravo AF: 0.157

Asia WGS AF: 0.0960 AC: 335 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.6
DANN	Benign	0.48
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2056726; hg19: chr7-99780283;