ENST00000557772.5:c.*219G>C

Variant names:

• chr14-64234738-C-G
• rs944460
• ENST00000557772.5:c.*219G>C

Variant summary

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

The ENST00000557772.5(ESR2):​c.*219G>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 0.0486 in 928,502 control chromosomes in the GnomAD database, including 2,787 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.056 (559 hom., cov: 32)
  • Exomes 𝑓: 0.047 (2228 hom.)
• Consequence: ESR2 ENST00000557772.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0160
• Publications: 8 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=-0.92).
• BP6: Variant 14-64234738-C-G is Benign according to our data. Variant chr14-64234738-C-G is described in ClinVar as Benign. ClinVar VariationId is 1282534.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.35 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	NM_001437.3	MANE Select	c.1406+232G>C		intron	N/A	NP_001428.1
	ESR2	NM_001040275.1		c.1406+232G>C		intron	N/A	NP_001035365.1
	ESR2	NM_001291712.2		c.1406+232G>C		intron	N/A	NP_001278641.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ESR2	ENST00000557772.5	TSL:1	c.*219G>C		3_prime_UTR	Exon 7 of 7	ENSP00000451582.1
	ESR2	ENST00000341099.6	TSL:1 MANE Select	c.1406+232G>C		intron	N/A	ENSP00000343925.4
	ESR2	ENST00000353772.7	TSL:1	c.1406+232G>C		intron	N/A	ENSP00000335551.4

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8477 AN: 152098 Hom.: 562 Cov.: 32

Gnomad AFR AF: 0.0534

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0110

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.0379

Gnomad FIN AF: 0.0883

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0365

Gnomad OTH AF: 0.0444

GnomAD4 exome AF: 0.0472 AC: 36641 AN: 776286 Hom.: 2228 Cov.: 10 AF XY: 0.0463 AC XY: 17926 AN XY: 387206

African (AFR) AF: 0.0519 AC: 967 AN: 18648

American (AMR) AF: 0.0365 AC: 680 AN: 18618

Ashkenazi Jewish (ASJ) AF: 0.0121 AC: 188 AN: 15500

East Asian (EAS) AF: 0.312 AC: 9998 AN: 32060

South Asian (SAS) AF: 0.0267 AC: 1207 AN: 45180

European-Finnish (FIN) AF: 0.0769 AC: 2232 AN: 29014

Middle Eastern (MID) AF: 0.0118 AC: 31 AN: 2628

European-Non Finnish (NFE) AF: 0.0335 AC: 19391 AN: 578042

Other (OTH) AF: 0.0532 AC: 1947 AN: 36596

GnomAD4 genome AF: 0.0557 AC: 8479 AN: 152216 Hom.: 559 Cov.: 32 AF XY: 0.0587 AC XY: 4371 AN XY: 74420

African (AFR) AF: 0.0533 AC: 2215 AN: 41524

American (AMR) AF: 0.0418 AC: 639 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0110 AC: 38 AN: 3470

East Asian (EAS) AF: 0.364 AC: 1880 AN: 5164

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4828

European-Finnish (FIN) AF: 0.0883 AC: 936 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0365 AC: 2482 AN: 68008

Other (OTH) AF: 0.0468 AC: 99 AN: 2116

Alfa AF: 0.0477 Hom.: 33

Bravo AF: 0.0528

Asia WGS AF: 0.167 AC: 579 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	-0.92
CADD	Benign	4.0
DANN	Benign	0.38
PhyloP100		0.016
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs944460; hg19: chr14-64701456;