Genetic Variant ESR2:c.*923C>A (chr14-64232214-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001437.3(ESR2):c.*923C>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 0.651 in 152,016 control chromosomes in the GnomAD database, including 33,860 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 0.65 ( 33857 hom., cov: 30)

Exomes 𝑓: 0.45 ( 3 hom. )

Consequence

ESR2
NM_001437.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.485

Publications

19 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:

LOC124903328 (HGNC:):

LOC124903328 links:

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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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ESR2	NM_001437.3 link	c.*923C>A		3_prime_UTR_variant	Exon 9 of 9	ENST00000341099.6	NP_001428.1	Q92731-1Q7LCB3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6 link	c.*923C>A		3_prime_UTR_variant	Exon 9 of 9	1	NM_001437.3	ENSP00000343925.4		Q92731-1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98894

AN:

151856

Hom.:

33807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.557

Gnomad ASJ

AF:

0.630

Gnomad EAS

AF:

0.691

Gnomad SAS

AF:

0.487

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.556

Gnomad OTH

AF:

0.629

GnomAD4 exome

AF:

0.452

AC:

AN:

Hom.:

Cov.:

AF XY:

0.417

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.429

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.651

AC:

98998

AN:

151974

Hom.:

33857

Cov.:

AF XY:

0.647

AC XY:

48067

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.877

AC:

36374

AN:

41474

American (AMR)

AF:

0.557

AC:

8499

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.630

AC:

2184

AN:

3466

East Asian (EAS)

AF:

0.691

AC:

3570

AN:

5164

South Asian (SAS)

AF:

0.486

AC:

2340

AN:

4810

European-Finnish (FIN)

AF:

0.577

AC:

6081

AN:

10548

Middle Eastern (MID)

AF:

0.541

AC:

159

AN:

294

European-Non Finnish (NFE)

AF:

0.556

AC:

37757

AN:

67930

Other (OTH)

AF:

0.628

AC:

1326

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1631

3263

4894

6526

8157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

776

1552

2328

3104

3880

<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:

0.718

Hom.:

9073

Bravo

AF:

0.664

Asia WGS

AF:

0.607

AC:

2112

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

(source)

DANN

Benign

0.30

PhyloP100

-0.48

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