14-64030045-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182914.3(SYNE2):c.6865T>C(p.Leu2289Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,613,850 control chromosomes in the GnomAD database, including 2,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 649 hom., cov: 33)

Exomes 𝑓: 0.046 ( 1967 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.00

Publications

6 publications found

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 Gene-Disease associations (from GenCC):

autosomal dominant Emery-Dreifuss muscular dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Emery-Dreifuss muscular dystrophy 5, autosomal dominant
Inheritance: AD, Unknown Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
left ventricular noncompaction
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SYNE2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 14-64030045-T-C is Benign according to our data. Variant chr14-64030045-T-C is described in ClinVar as [Benign]. Clinvar id is 130505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.6865T>C	p.Leu2289Leu	synonymous_variant	Exon 44 of 116	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6 link	c.6865T>C	p.Leu2289Leu	synonymous_variant	Exon 44 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12047

AN:

151974

Hom.:

643

Cov.:

show subpopulations

Gnomad AFR

AF:

0.149

Gnomad AMI

AF:

0.0406

Gnomad AMR

AF:

0.0922

Gnomad ASJ

AF:

0.0493

Gnomad EAS

AF:

0.0519

Gnomad SAS

AF:

0.0382

Gnomad FIN

AF:

0.0620

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0436

Gnomad OTH

AF:

0.0767

GnomAD2 exomes

AF:

0.0584

AC:

14564

AN:

249388

AF XY:

0.0539

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.103

Gnomad ASJ exome

AF:

0.0483

Gnomad EAS exome

AF:

0.0526

Gnomad FIN exome

AF:

0.0524

Gnomad NFE exome

AF:

0.0402

Gnomad OTH exome

AF:

0.0518

GnomAD4 exome

AF:

0.0457

AC:

66861

AN:

1461758

Hom.:

1967

Cov.:

AF XY:

0.0452

AC XY:

32846

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.152

AC:

5087

AN:

33478

American (AMR)

AF:

0.103

AC:

4619

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0458

AC:

1198

AN:

26132

East Asian (EAS)

AF:

0.0567

AC:

2251

AN:

39686

South Asian (SAS)

AF:

0.0391

AC:

3375

AN:

86250

European-Finnish (FIN)

AF:

0.0510

AC:

2723

AN:

53408

Middle Eastern (MID)

AF:

0.0324

AC:

187

AN:

5766

European-Non Finnish (NFE)

AF:

0.0399

AC:

44398

AN:

1111928

Other (OTH)

AF:

0.0501

AC:

3023

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

3633

7266

10900

14533

18166

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0794

AC:

12072

AN:

152092

Hom.:

649

Cov.:

AF XY:

0.0790

AC XY:

5876

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.149

AC:

6194

AN:

41454

American (AMR)

AF:

0.0921

AC:

1408

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0493

AC:

171

AN:

3470

East Asian (EAS)

AF:

0.0521

AC:

270

AN:

5186

South Asian (SAS)

AF:

0.0382

AC:

184

AN:

4814

European-Finnish (FIN)

AF:

0.0620

AC:

656

AN:

10574

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0436

AC:

2965

AN:

67992

Other (OTH)

AF:

0.0773

AC:

163

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

533

1067

1600

2134

2667

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0567

Hom.:

295

Bravo

AF:

0.0837

Asia WGS

AF:

0.0550

AC:

191

AN:

3476

EpiCase

AF:

0.0382

EpiControl

AF:

0.0398

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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:1

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

4.9

(source)

DANN

Benign

0.65

PhyloP100

-1.0

Mutation Taster

=294/6

polymorphism (auto)

(source)

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

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14-64030045-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over