dbSNP rs58262369: ESR2:c.*339G>A (chr14-64227194-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0300

Publications

11 publications found

Variant links:

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)

ESR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ESR2	NR_073496.2 link	n.2494G>A	non_coding_transcript_exon_variant	Exon 8 of 8
ESR2	NM_001040275.1 link	c.*339G>A	3_prime_UTR_variant	Exon 9 of 9	NP_001035365.1
ESR2	NM_001291712.2 link	c.*339G>A	3_prime_UTR_variant	Exon 14 of 14	NP_001278641.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
ESR2	ENST00000353772.7 link	c.*339G>A	3_prime_UTR_variant	Exon 9 of 9	1	ENSP00000335551.4
ESR2	ENST00000554572.5 link	c.*339G>A	3_prime_UTR_variant	Exon 14 of 14	1	ENSP00000450699.1
ESR2	ENST00000556275.5 link	c.1406+7776G>A	intron_variant	Intron 8 of 8	2	ENSP00000452485.2
ESR2	ENST00000358599.9 link	c.*339G>A	downstream_gene_variant		2	ENSP00000351412.5

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3680

AN:

152226

Hom.:

117

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.00945

AC XY:

762

AN XY:

80616

show subpopulations

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:

AN:

5050

East Asian (EAS)

AF:

0.0725

AC:

577

AN:

7954

South Asian (SAS)

AF:

0.00133

AC:

AN:

13556

European-Finnish (FIN)

AF:

0.00418

AC:

AN:

8372

Middle Eastern (MID)

AF:

0.00130

AC:

AN:

770

European-Non Finnish (NFE)

AF:

0.000795

AC:

AN:

100604

Other (OTH)

AF:

0.0134

AC:

129

AN:

9650

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

146

219

292

365

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0242

AC:

3692

AN:

152344

Hom.:

119

Cov.:

AF XY:

0.0244

AC XY:

1821

AN XY:

74492

show subpopulations

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:

AN:

3468

East Asian (EAS)

AF:

0.0922

AC:

478

AN:

5186

South Asian (SAS)

AF:

0.00228

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00546

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000647

AC:

AN:

68036

Other (OTH)

AF:

0.0312

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

171

342

514

685

856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0238

Hom.:

Bravo

AF:

0.0335

Asia WGS

AF:

0.0380

AC:

133

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.8

(source)

DANN

Benign

0.52

PhyloP100

-0.030

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over