14-64227153-G-C

Variant names:

• chr14-64227153-G-C
• rs1255998
• ENST00000353772.7:c.*380C>G

Variant summary

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

The NM_001040275.1(ESR2):​c.*380C>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 0.211 in 233,964 control chromosomes in the GnomAD database, including 9,064 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 0.25 (7833 hom., cov: 32)
  • Exomes 𝑓: 0.13 (1231 hom.)
• Consequence: ESR2 NM_001040275.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.260
• Publications: 39 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040275.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NM_001040275.1		c.*380C>G		3_prime_UTR	Exon 9 of 9	NP_001035365.1	Q92731-2
	ESR2	NM_001291712.2		c.*380C>G		3_prime_UTR	Exon 14 of 14	NP_001278641.1	Q92731-2
	ESR2	NM_001291723.1		c.*380C>G		3_prime_UTR	Exon 9 of 9	NP_001278652.1	Q92731-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000353772.7	TSL:1	c.*380C>G		3_prime_UTR	Exon 9 of 9	ENSP00000335551.4	Q92731-2
	ESR2	ENST00000554572.5	TSL:1	c.*380C>G		3_prime_UTR	Exon 14 of 14	ENSP00000450699.1	Q92731-2
	ESR2	ENST00000556275.5	TSL:2	c.1406+7817C>G		intron	N/A	ENSP00000452485.2	G3V5S2

Frequencies

GnomAD3 genomes AF: 0.253 AC: 38512 AN: 151976 Hom.: 7818 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.171

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.234

GnomAD4 exome AF: 0.133 AC: 10860 AN: 81870 Hom.: 1231 Cov.: 0 AF XY: 0.133 AC XY: 5585 AN XY: 42130

African (AFR) AF: 0.508 AC: 1004 AN: 1978

American (AMR) AF: 0.220 AC: 778 AN: 3530

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 400 AN: 2690

East Asian (EAS) AF: 0.449 AC: 1568 AN: 3494

South Asian (SAS) AF: 0.141 AC: 887 AN: 6280

European-Finnish (FIN) AF: 0.106 AC: 445 AN: 4200

Middle Eastern (MID) AF: 0.127 AC: 48 AN: 378

European-Non Finnish (NFE) AF: 0.0909 AC: 4926 AN: 54210

Other (OTH) AF: 0.157 AC: 804 AN: 5110

GnomAD4 genome AF: 0.254 AC: 38576 AN: 152094 Hom.: 7833 Cov.: 32 AF XY: 0.254 AC XY: 18867 AN XY: 74342

African (AFR) AF: 0.537 AC: 22247 AN: 41454

American (AMR) AF: 0.223 AC: 3404 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2902 AN: 5168

South Asian (SAS) AF: 0.170 AC: 820 AN: 4824

European-Finnish (FIN) AF: 0.122 AC: 1295 AN: 10586

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6815 AN: 67984

Other (OTH) AF: 0.234 AC: 495 AN: 2112

Alfa AF: 0.0547 Hom.: 71

Bravo AF: 0.277

Asia WGS AF: 0.332 AC: 1151 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.58
PhyloP100		-0.26
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: rs1255998; hg19: chr14-64693871;