14-64294095-AG-AGG

Position:

• chr14-64294095-AG-AGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001437.3(ESR2):​c.-154dupC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 152,378 control chromosomes in the GnomAD database, including 81 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (81 hom., cov: 33)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: ESR2 NM_001437.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0890

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0884 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ESR2	NM_001437.3	c.-154dupC		5_prime_UTR_variant	1/9	ENST00000341099.6	NP_001428.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ESR2	ENST00000341099.6	c.-154dupC		5_prime_UTR_variant	1/9	1	NM_001437.3	ENSP00000343925.4

Frequencies

GnomAD3 genomes AF: 0.0184 AC: 2801 AN: 152168 Hom.: 80 Cov.: 33

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0609

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.00642

Gnomad FIN AF: 0.00697

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00215

Gnomad OTH AF: 0.0307

GnomAD4 exome AF: 0.0213 AC: 2 AN: 94 Hom.: 0 Cov.: 0 AF XY: 0.0147 AC XY: 1 AN XY: 68

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.0185 AC: 2812 AN: 152284 Hom.: 81 Cov.: 33 AF XY: 0.0193 AC XY: 1438 AN XY: 74466

Gnomad4 AFR AF: 0.0255

Gnomad4 AMR AF: 0.0612

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0954

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00697

Gnomad4 NFE AF: 0.00215

Gnomad4 OTH AF: 0.0313

Bravo AF: 0.0265

Asia WGS AF: 0.0560 AC: 195 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832949; hg19: chr14-64760813;