rs2297301

Positions:

chr14-64177487-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182914.3(SYNE2):c.17556+4T>C variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 1,614,116 control chromosomes in the GnomAD database, including 974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 76 hom., cov: 32)

Exomes 𝑓: 0.026 ( 898 hom. )

Consequence

SYNE2
NM_182914.3 splice_donor_region, intron

Scores

Splicing: ADA: 0.0005099

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.265

Variant links:

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]

SYNE2 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 14-64177487-T-C is Benign according to our data. Variant chr14-64177487-T-C is described in ClinVar as [Benign]. Clinvar id is 130487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64177487-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.17556+4T>C		splice_donor_region_variant, intron_variant		ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.17556+4T>C		splice_donor_region_variant, intron_variant		1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3344

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0469

Gnomad FIN

AF:

0.0440

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0221

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0299

AC:

7512

AN:

251278

Hom.:

207

AF XY:

0.0305

AC XY:

4141

AN XY:

135852

show subpopulations

Gnomad AFR exome

AF:

0.00463

Gnomad AMR exome

AF:

0.00708

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.121

Gnomad SAS exome

AF:

0.0372

Gnomad FIN exome

AF:

0.0433

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0232

GnomAD4 exome

AF:

0.0258

AC:

37747

AN:

1461818

Hom.:

898

Cov.:

AF XY:

0.0260

AC XY:

18929

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00403

Gnomad4 AMR exome

AF:

0.00850

Gnomad4 ASJ exome

AF:

0.0110

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.0375

Gnomad4 FIN exome

AF:

0.0446

Gnomad4 NFE exome

AF:

0.0217

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0219

AC:

3341

AN:

152298

Hom.:

Cov.:

AF XY:

0.0232

AC XY:

1730

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00467

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0473

Gnomad4 FIN

AF:

0.0440

Gnomad4 NFE

AF:

0.0221

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.0190

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.0780

AC:

269

AN:

3478

EpiCase

AF:

0.0196

EpiControl

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:3

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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

-0.77

CADD

Benign

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00051

dbscSNV1_RF

Benign

0.092

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over