rs57018718

Positions:

• chr14-64127301-G-A
• chr14-64127301-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182914.3(SYNE2):​c.13917+494G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0678 in 151,938 control chromosomes in the GnomAD database, including 433 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 0.068 (433 hom., cov: 32)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

SYNE2 (HGNC:17084): (spectrin repeat containing nuclear envelope protein 2) The protein encoded by this gene is a nuclear outer membrane protein that binds cytoplasmic F-actin. This binding tethers the nucleus to the cytoskeleton and aids in the maintenance of the structural integrity of the nucleus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3	c.13917+494G>A		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6	c.13917+494G>A		intron_variant		1	NM_182914.3	P4

Frequencies

GnomAD3 genomes AF: 0.0679 AC: 10302 AN: 151820 Hom.: 436 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0729

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.0990

Gnomad FIN AF: 0.0197

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0383

Gnomad OTH AF: 0.0746

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0678 AC: 10302 AN: 151938 Hom.: 433 Cov.: 32 AF XY: 0.0686 AC XY: 5093 AN XY: 74266

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.0728

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.0197

Gnomad4 NFE AF: 0.0383

Gnomad4 OTH AF: 0.0743

Alfa AF: 0.0244 Hom.: 14

Bravo AF: 0.0720

Asia WGS AF: 0.102 AC: 355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.42
DANN	Benign	0.56

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: rs57018718; hg19: chr14-64594019;