dbSNP rs17101774: ESR2:c.-768+9550A>G (chr14-64326863-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000554572.5(ESR2):c.-768+9550A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0446 in 152,304 control chromosomes in the GnomAD database, including 319 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 0.045 ( 319 hom., cov: 32)

Consequence

ESR2
ENST00000554572.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.71

Publications

4 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=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein
ESR2	NM_001291712.2 link	c.-768+9550A>G	intron_variant	Intron 2 of 13	NP_001278641.1
ESR2	NM_001291723.1 link	c.-91+11035A>G	intron_variant	Intron 1 of 8	NP_001278652.1
ESR2	NR_073496.2 link	n.716+11035A>G	intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000554572.5 link	c.-768+9550A>G		intron_variant	Intron 2 of 13	1		ENSP00000450699.1
ESR2	ENST00000358599.9 link	c.-91+11035A>G		intron_variant	Intron 1 of 8	2		ENSP00000351412.5

Frequencies

GnomAD3 genomes

AF:

0.0445

AC:

6776

AN:

152186

Hom.:

317

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.0211

Gnomad ASJ

AF:

0.0426

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0242

Gnomad FIN

AF:

0.00593

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0177

Gnomad OTH

AF:

0.0377

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

GnomAD4 genome

AF:

0.0446

AC:

6788

AN:

152304

Hom.:

319

Cov.:

AF XY:

0.0432

AC XY:

3216

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.116

AC:

4814

AN:

41544

American (AMR)

AF:

0.0211

AC:

322

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0426

AC:

148

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5194

South Asian (SAS)

AF:

0.0242

AC:

117

AN:

4828

European-Finnish (FIN)

AF:

0.00593

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0177

AC:

1204

AN:

68028

Other (OTH)

AF:

0.0373

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

314

627

941

1254

1568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0286

Hom.:

169

Bravo

AF:

0.0489

Asia WGS

AF:

0.0160

AC:

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

0.13

(source)

DANN

Benign

0.46

PhyloP100

-1.7

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over