14-64126489-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182914.3(SYNE2):c.13707+10T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,614,110 control chromosomes in the GnomAD database, including 276 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 46 hom., cov: 32)

Exomes 𝑓: 0.017 ( 230 hom. )

Consequence

SYNE2
NM_182914.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.947

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=-0.87).

BP6

Variant 14-64126489-T-C is Benign according to our data. Variant chr14-64126489-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 313591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64126489-T-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0225 (3433/152290) while in subpopulation AFR AF= 0.0372 (1546/41542). AF 95% confidence interval is 0.0357. There are 46 homozygotes in gnomad4. There are 1699 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3433 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.13707+10T>C		intron_variant	Intron 72 of 115	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6 link	c.13707+10T>C		intron_variant	Intron 72 of 115	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0225

AC:

3427

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0189

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0227

Gnomad FIN

AF:

0.0284

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0153

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0168

AC:

4213

AN:

251078

Hom.:

AF XY:

0.0171

AC XY:

2326

AN XY:

135696

show subpopulations

Gnomad AFR exome

AF:

0.0385

Gnomad AMR exome

AF:

0.00738

Gnomad ASJ exome

AF:

0.0180

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0226

Gnomad FIN exome

AF:

0.0255

Gnomad NFE exome

AF:

0.0157

Gnomad OTH exome

AF:

0.0196

GnomAD4 exome

AF:

0.0166

AC:

24222

AN:

1461820

Hom.:

230

Cov.:

AF XY:

0.0167

AC XY:

12115

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0380

Gnomad4 AMR exome

AF:

0.00778

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.000302

Gnomad4 SAS exome

AF:

0.0219

Gnomad4 FIN exome

AF:

0.0258

Gnomad4 NFE exome

AF:

0.0158

Gnomad4 OTH exome

AF:

0.0192

GnomAD4 genome

AF:

0.0225

AC:

3433

AN:

152290

Hom.:

Cov.:

AF XY:

0.0228

AC XY:

1699

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0372

Gnomad4 AMR

AF:

0.0188

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0228

Gnomad4 FIN

AF:

0.0284

Gnomad4 NFE

AF:

0.0153

Gnomad4 OTH

AF:

0.0189

Alfa

AF:

0.00964

Hom.:

Bravo

AF:

0.0222

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:3

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified

Benign:2

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 10, 2024

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Jul 10, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.012

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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