14-64234021-A-G

Variant names:

• chr14-64234021-A-G
• rs1256064
• ENST00000557772.5:c.*936T>C

Variant summary

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

The ENST00000557772.5(ESR2):​c.*936T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,074 control chromosomes in the GnomAD database, including 7,348 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 (7347 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: ESR2 ENST00000557772.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000557772.5. 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	NM_001437.3	MANE Select	c.1407-698T>C		intron	N/A	NP_001428.1
	ESR2	NM_001040275.1		c.1406+949T>C		intron	N/A	NP_001035365.1
	ESR2	NM_001291712.2		c.1406+949T>C		intron	N/A	NP_001278641.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000557772.5	TSL:1	c.*936T>C		3_prime_UTR	Exon 7 of 7	ENSP00000451582.1
	ESR2	ENST00000341099.6	TSL:1 MANE Select	c.1407-698T>C		intron	N/A	ENSP00000343925.4
	ESR2	ENST00000353772.7	TSL:1	c.1406+949T>C		intron	N/A	ENSP00000335551.4

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37702 AN: 151926 Hom.: 7337 Cov.: 32

Gnomad AFR AF: 0.515

Gnomad AMI AF: 0.0680

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.231

GnomAD4 exome AF: 0.100 AC: 3 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.150 AC XY: 3 AN XY: 20

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0417 AC: 1 AN: 24

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.248 AC: 37753 AN: 152044 Hom.: 7347 Cov.: 32 AF XY: 0.249 AC XY: 18513 AN XY: 74334

African (AFR) AF: 0.514 AC: 21305 AN: 41412

American (AMR) AF: 0.222 AC: 3393 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 503 AN: 3462

East Asian (EAS) AF: 0.554 AC: 2858 AN: 5160

South Asian (SAS) AF: 0.164 AC: 790 AN: 4816

European-Finnish (FIN) AF: 0.124 AC: 1315 AN: 10584

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.103 AC: 7001 AN: 68012

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.152 Hom.: 11885

Bravo AF: 0.271

Asia WGS AF: 0.322 AC: 1119 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.59
PhyloP100		0.093
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1256064; hg19: chr14-64700739;