rs11847087

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182914.3(SYNE2):c.9389A>G(p.Asn3130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,608,316 control chromosomes in the GnomAD database, including 2,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 585 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1577 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.891

Publications

16 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013741553).

BP6

Variant 14-64053302-A-G is Benign according to our data. Variant chr14-64053302-A-G is described in ClinVar as Benign. ClinVar VariationId is 130519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.9389A>G	p.Asn3130Ser	missense_variant	Exon 48 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.9389A>G	p.Asn3130Ser	missense_variant	Exon 48 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0699

AC:

10642

AN:

152158

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0406

Gnomad OTH

AF:

0.0641

GnomAD2 exomes

AF:

0.0404

AC:

9861

AN:

244102

AF XY:

0.0381

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0305

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0423

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0399

AC:

58062

AN:

1456040

Hom.:

1577

Cov.:

AF XY:

0.0389

AC XY:

28155

AN XY:

723852

show subpopulations

African (AFR)

AF:

0.161

AC:

5305

AN:

32996

American (AMR)

AF:

0.0328

AC:

1429

AN:

43620

Ashkenazi Jewish (ASJ)

AF:

0.0613

AC:

1593

AN:

26004

East Asian (EAS)

AF:

0.00

AC:

AN:

39652

South Asian (SAS)

AF:

0.00890

AC:

749

AN:

84142

European-Finnish (FIN)

AF:

0.0256

AC:

1366

AN:

53340

Middle Eastern (MID)

AF:

0.0758

AC:

436

AN:

5752

European-Non Finnish (NFE)

AF:

0.0401

AC:

44477

AN:

1110406

Other (OTH)

AF:

0.0450

AC:

2707

AN:

60128

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

2945

5891

8836

11782

14727

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1676

3352

5028

6704

8380

<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:

0.0701

AC:

10673

AN:

152276

Hom.:

585

Cov.:

AF XY:

0.0687

AC XY:

5113

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.154

AC:

6415

AN:

41542

American (AMR)

AF:

0.0450

AC:

688

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0631

AC:

219

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00829

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0267

AC:

284

AN:

10618

Middle Eastern (MID)

AF:

0.116

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0406

AC:

2765

AN:

68024

Other (OTH)

AF:

0.0639

AC:

135

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

477

954

1432

1909

2386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0504

Hom.:

1271

Bravo

AF:

0.0759

TwinsUK

AF:

0.0369

AC:

137

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.144

AC:

522

ESP6500EA

AF:

0.0406

AC:

330

ExAC

AF:

0.0418

AC:

5043

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0429

EpiControl

AF:

0.0439

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 14, 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

- -

SYNE2-related disorder

Benign:1

Jan 20, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.8

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

.;T;T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.78

T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.

PhyloP100

0.89

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.031

Sift

Benign

0.21

T;.;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.021

B;.;B;.

Vest4

0.13

MPC

0.043

ClinPred

0.0097

GERP RS

3.0

Varity_R

0.029

gMVP

0.15

Mutation Taster

=295/5

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