ENST00000353772.7:c.*339G>A

Variant names:

• chr14-64227194-C-T
• rs58262369
• ENST00000353772.7:c.*339G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000353772.7(ESR2):​c.*339G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 308,098 control chromosomes in the GnomAD database, including 180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.024 (119 hom., cov: 32)
  • Exomes 𝑓: 0.0099 (61 hom.)
• Consequence: ESR2 ENST00000353772.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 11 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0853 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000353772.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NR_073496.2		n.2494G>A		non_coding_transcript_exon	Exon 8 of 8
	ESR2	NM_001040275.1		c.*339G>A		3_prime_UTR	Exon 9 of 9	NP_001035365.1
	ESR2	NM_001291712.2		c.*339G>A		3_prime_UTR	Exon 14 of 14	NP_001278641.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000353772.7	TSL:1	c.*339G>A		3_prime_UTR	Exon 9 of 9	ENSP00000335551.4
	ESR2	ENST00000554572.5	TSL:1	c.*339G>A		3_prime_UTR	Exon 14 of 14	ENSP00000450699.1
	ESR2	ENST00000556275.5	TSL:2	c.1406+7776G>A		intron	N/A	ENSP00000452485.2

Frequencies

GnomAD3 genomes AF: 0.0242 AC: 3680 AN: 152226 Hom.: 117 Cov.: 32

Gnomad AFR AF: 0.0497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0626

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.0922

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00546

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.00994 AC: 1548 AN: 155754 Hom.: 61 Cov.: 0 AF XY: 0.00945 AC XY: 762 AN XY: 80616

African (AFR) AF: 0.0443 AC: 182 AN: 4104

American (AMR) AF: 0.0919 AC: 523 AN: 5694

Ashkenazi Jewish (ASJ) AF: 0.000594 AC: 3 AN: 5050

East Asian (EAS) AF: 0.0725 AC: 577 AN: 7954

South Asian (SAS) AF: 0.00133 AC: 18 AN: 13556

European-Finnish (FIN) AF: 0.00418 AC: 35 AN: 8372

Middle Eastern (MID) AF: 0.00130 AC: 1 AN: 770

European-Non Finnish (NFE) AF: 0.000795 AC: 80 AN: 100604

Other (OTH) AF: 0.0134 AC: 129 AN: 9650

GnomAD4 genome AF: 0.0242 AC: 3692 AN: 152344 Hom.: 119 Cov.: 32 AF XY: 0.0244 AC XY: 1821 AN XY: 74492

African (AFR) AF: 0.0497 AC: 2067 AN: 41572

American (AMR) AF: 0.0629 AC: 962 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3468

East Asian (EAS) AF: 0.0922 AC: 478 AN: 5186

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4832

European-Finnish (FIN) AF: 0.00546 AC: 58 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68036

Other (OTH) AF: 0.0312 AC: 66 AN: 2116

Alfa AF: 0.0238 Hom.: 88

Bravo AF: 0.0335

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		-0.030
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs58262369; hg19: chr14-64693912;