14-63942134-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_182914.3(SYNE2):c.399G>C(p.Leu133Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,578,694 control chromosomes in the GnomAD database, including 6,239 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L133L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.11 ( 1276 hom., cov: 32)

Exomes 𝑓: 0.076 ( 4963 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.888

Publications

8 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 14-63942134-G-C is Benign according to our data. Variant chr14-63942134-G-C is described in ClinVar as Benign. ClinVar VariationId is 130496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.888 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.399G>C	p.Leu133Leu	synonymous_variant	Exon 6 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.399G>C	p.Leu133Leu	synonymous_variant	Exon 6 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16844

AN:

151998

Hom.:

1271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.0521

Gnomad SAS

AF:

0.0387

Gnomad FIN

AF:

0.0375

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0734

Gnomad OTH

AF:

0.0891

GnomAD2 exomes

AF:

0.0847

AC:

21015

AN:

248130

AF XY:

0.0776

show subpopulations

Gnomad AFR exome

AF:

0.222

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.0515

Gnomad EAS exome

AF:

0.0414

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0717

Gnomad OTH exome

AF:

0.0738

GnomAD4 exome

AF:

0.0761

AC:

108526

AN:

1426578

Hom.:

4963

Cov.:

AF XY:

0.0738

AC XY:

52550

AN XY:

711984

show subpopulations

African (AFR)

AF:

0.221

AC:

7176

AN:

32530

American (AMR)

AF:

0.158

AC:

7054

AN:

44662

Ashkenazi Jewish (ASJ)

AF:

0.0515

AC:

1336

AN:

25946

East Asian (EAS)

AF:

0.0734

AC:

2899

AN:

39482

South Asian (SAS)

AF:

0.0377

AC:

3226

AN:

85630

European-Finnish (FIN)

AF:

0.0434

AC:

2256

AN:

51946

Middle Eastern (MID)

AF:

0.0255

AC:

145

AN:

5688

European-Non Finnish (NFE)

AF:

0.0741

AC:

80112

AN:

1081446

Other (OTH)

AF:

0.0729

AC:

4322

AN:

59248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

4356

8712

13068

17424

21780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3068

6136

9204

12272

15340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.111

AC:

16870

AN:

152116

Hom.:

1276

Cov.:

AF XY:

0.108

AC XY:

8009

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.212

AC:

8769

AN:

41444

American (AMR)

AF:

0.120

AC:

1837

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3470

East Asian (EAS)

AF:

0.0519

AC:

269

AN:

5186

South Asian (SAS)

AF:

0.0383

AC:

185

AN:

4826

European-Finnish (FIN)

AF:

0.0375

AC:

397

AN:

10598

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0734

AC:

4991

AN:

68004

Other (OTH)

AF:

0.0882

AC:

186

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

743

1486

2229

2972

3715

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

168

336

504

672

840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0801

Hom.:

198

Bravo

AF:

0.124

Asia WGS

AF:

0.0600

AC:

210

AN:

3478

EpiCase

AF:

0.0685

EpiControl

AF:

0.0644

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 09, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:2

Feb 03, 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

-0.46

CADD

Benign

(source)

DANN

Benign

0.81

PhyloP100

0.89

Mutation Taster

=215/85

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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