rs915057

chr14-64219489-A-Gchr14-64219489-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182914.3(SYNE2):c.19860+79A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,419,412 control chromosomes in the GnomAD database, including 245,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.66 (34862 hom., cov: 32)
  • Exomes 𝑓: 0.57 (211045 hom.)
• Consequence: SYNE2 NM_182914.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.04

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 14-64219489-A-G is Benign according to our data. Variant chr14-64219489-A-G is described in ClinVar as [Benign]. Clinvar id is 1270010.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3	c.19860+79A>G		intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6	c.19860+79A>G		intron_variant		1	NM_182914.3	P4

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100603 AN: 151986 Hom.: 34811 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.782

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.635

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.640

GnomAD4 exome AF: 0.572 AC: 725127 AN: 1267308 Hom.: 211045 AF XY: 0.568 AC XY: 362141 AN XY: 637442

Gnomad4 AFR exome AF: 0.889

Gnomad4 AMR exome AF: 0.534

Gnomad4 ASJ exome AF: 0.634

Gnomad4 EAS exome AF: 0.681

Gnomad4 SAS exome AF: 0.484

Gnomad4 FIN exome AF: 0.568

Gnomad4 NFE exome AF: 0.564

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.662 AC: 100709 AN: 152104 Hom.: 34862 Cov.: 32 AF XY: 0.657 AC XY: 48859 AN XY: 74346

Gnomad4 AFR AF: 0.881

Gnomad4 AMR AF: 0.564

Gnomad4 ASJ AF: 0.635

Gnomad4 EAS AF: 0.728

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.578

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.639

Alfa AF: 0.633 Hom.: 4578

Bravo AF: 0.675

Asia WGS AF: 0.622 AC: 2164 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.031
Dann	Benign	0.16

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: rs915057; hg19: chr14-64686207; COSMIC: COSV59958466; COSMIC: COSV59958466;