ENST00000554572.5:c.-91+2333_-91+2334insGG

Variant names:

• chr14-64295199-A-ACC
• rs3841304
• ENST00000554572.5:c.-91+2333_-91+2334insGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000554572.5(ESR2):​c.-91+2333_-91+2334insGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 146,306 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000041 (0 hom., cov: 30)
• Consequence: ESR2 ENST00000554572.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 1 publications found

Genes affected

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center
• familial medullary thyroid carcinoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• ovarian dysgenesis 8

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001291712.2	c.-91+2332_-91+2333dupGG		intron_variant	Intron 6 of 13		NP_001278641.1
ESR2	NM_001291723.1	c.-90-12126_-90-12125dupGG		intron_variant	Intron 1 of 8		NP_001278652.1
ESR2	NR_073496.2	n.717-12126_717-12125dupGG		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5	c.-91+2333_-91+2334insGG		intron_variant	Intron 6 of 13	1		ENSP00000450699.1
ESR2	ENST00000358599.9	c.-90-12125_-90-12124insGG		intron_variant	Intron 1 of 8	2		ENSP00000351412.5

Frequencies

GnomAD3 genomes AF: 0.0000410 AC: 6 AN: 146192 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000260

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000673

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000603

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000410 AC: 6 AN: 146306 Hom.: 0 Cov.: 30 AF XY: 0.0000419 AC XY: 3 AN XY: 71582

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000259 AC: 1 AN: 38536

American (AMR) AF: 0.0000673 AC: 1 AN: 14868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3328

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.0000604 AC: 4 AN: 66274

Other (OTH) AF: 0.00 AC: 0 AN: 1996

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.00343940), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.12

Splicing

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

Other links and lift over

dbSNP: rs3841304; hg19: chr14-64761917;