rs8018687

Variant names:

• chr14-64227364-T-C
• rs8018687
• ENST00000353772.7:c.*169A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000353772.7(ESR2):​c.*169A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0999 in 697,990 control chromosomes in the GnomAD database, including 6,727 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (3746 hom., cov: 32)
  • Exomes 𝑓: 0.082 (2981 hom.)
• Consequence: ESR2 ENST00000353772.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0130
• Publications: 13 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)

LOC124903328 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 14-64227364-T-C is Benign according to our data. Variant chr14-64227364-T-C is described in ClinVar as Benign. ClinVar VariationId is 1237589.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.399 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.2324A>G		non_coding_transcript_exon	Exon 8 of 8
	ESR2	NM_001040275.1		c.*169A>G		3_prime_UTR	Exon 9 of 9	NP_001035365.1
	ESR2	NM_001291712.2		c.*169A>G		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.*169A>G		3_prime_UTR	Exon 9 of 9	ENSP00000335551.4
	ESR2	ENST00000554572.5	TSL:1	c.*169A>G		3_prime_UTR	Exon 14 of 14	ENSP00000450699.1
	ESR2	ENST00000556275.5	TSL:2	c.1406+7606A>G		intron	N/A	ENSP00000452485.2

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25085 AN: 152104 Hom.: 3739 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.0980

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.0629

Gnomad OTH AF: 0.154

GnomAD4 exome AF: 0.0817 AC: 44581 AN: 545768 Hom.: 2981 Cov.: 7 AF XY: 0.0835 AC XY: 23823 AN XY: 285240

African (AFR) AF: 0.410 AC: 5740 AN: 13998

American (AMR) AF: 0.0949 AC: 1763 AN: 18574

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 1974 AN: 14360

East Asian (EAS) AF: 0.0764 AC: 2420 AN: 31658

South Asian (SAS) AF: 0.133 AC: 6139 AN: 46282

European-Finnish (FIN) AF: 0.0320 AC: 992 AN: 30998

Middle Eastern (MID) AF: 0.128 AC: 462 AN: 3620

European-Non Finnish (NFE) AF: 0.0619 AC: 22086 AN: 357050

Other (OTH) AF: 0.103 AC: 3005 AN: 29228

GnomAD4 genome AF: 0.165 AC: 25131 AN: 152222 Hom.: 3746 Cov.: 32 AF XY: 0.162 AC XY: 12064 AN XY: 74424

African (AFR) AF: 0.404 AC: 16762 AN: 41502

American (AMR) AF: 0.116 AC: 1773 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 461 AN: 3472

East Asian (EAS) AF: 0.0985 AC: 511 AN: 5190

South Asian (SAS) AF: 0.132 AC: 633 AN: 4812

European-Finnish (FIN) AF: 0.0285 AC: 302 AN: 10610

Middle Eastern (MID) AF: 0.133 AC: 39 AN: 294

European-Non Finnish (NFE) AF: 0.0629 AC: 4281 AN: 68018

Other (OTH) AF: 0.152 AC: 321 AN: 2112

Alfa AF: 0.106 Hom.: 2011

Bravo AF: 0.181

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.41
PhyloP100		-0.013
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: rs8018687; hg19: chr14-64694082; COSMIC: COSV59939092; COSMIC: COSV59939092;