14-64052317-A-G

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.8404A>G(p.Ser2802Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,614,086 control chromosomes in the GnomAD database, including 694,149 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2802N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.91 ( 63034 hom., cov: 32)

Exomes 𝑓: 0.93 ( 631115 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -1.59

Publications

41 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=9.721277E-7).

BP6

Variant 14-64052317-A-G is Benign according to our data. Variant chr14-64052317-A-G is described in ClinVar as Benign. ClinVar VariationId is 130513.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.8404A>G	p.Ser2802Gly	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.8404A>G	p.Ser2802Gly	missense_variant	Exon 48 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.909

AC:

138301

AN:

152120

Hom.:

62983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.868

Gnomad AMI

AF:

0.995

Gnomad AMR

AF:

0.918

Gnomad ASJ

AF:

0.827

Gnomad EAS

AF:

0.860

Gnomad SAS

AF:

0.814

Gnomad FIN

AF:

0.943

Gnomad MID

AF:

0.889

Gnomad NFE

AF:

0.940

Gnomad OTH

AF:

0.904

GnomAD2 exomes

AF:

0.908

AC:

226629

AN:

249470

AF XY:

0.905

show subpopulations

Gnomad AFR exome

AF:

0.868

Gnomad AMR exome

AF:

0.951

Gnomad ASJ exome

AF:

0.820

Gnomad EAS exome

AF:

0.844

Gnomad FIN exome

AF:

0.943

Gnomad NFE exome

AF:

0.937

Gnomad OTH exome

AF:

0.899

GnomAD4 exome

AF:

0.928

AC:

1357122

AN:

1461848

Hom.:

631115

Cov.:

AF XY:

0.925

AC XY:

672636

AN XY:

727228

show subpopulations

African (AFR)

AF:

0.864

AC:

28930

AN:

33480

American (AMR)

AF:

0.947

AC:

42346

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.815

AC:

21293

AN:

26134

East Asian (EAS)

AF:

0.867

AC:

34418

AN:

39698

South Asian (SAS)

AF:

0.827

AC:

71342

AN:

86254

European-Finnish (FIN)

AF:

0.942

AC:

50337

AN:

53416

Middle Eastern (MID)

AF:

0.896

AC:

5168

AN:

5768

European-Non Finnish (NFE)

AF:

0.943

AC:

1048328

AN:

1111986

Other (OTH)

AF:

0.910

AC:

54960

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

6201

12402

18604

24805

31006

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21576

43152

64728

86304

107880

<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:

0.909

AC:

138411

AN:

152238

Hom.:

63034

Cov.:

AF XY:

0.907

AC XY:

67524

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.869

AC:

36065

AN:

41520

American (AMR)

AF:

0.918

AC:

14042

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.827

AC:

2872

AN:

3472

East Asian (EAS)

AF:

0.860

AC:

4457

AN:

5182

South Asian (SAS)

AF:

0.814

AC:

3922

AN:

4816

European-Finnish (FIN)

AF:

0.943

AC:

10013

AN:

10614

Middle Eastern (MID)

AF:

0.884

AC:

260

AN:

294

European-Non Finnish (NFE)

AF:

0.940

AC:

63967

AN:

68026

Other (OTH)

AF:

0.903

AC:

1906

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

635

1270

1906

2541

3176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

904

1808

2712

3616

4520

<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:

0.924

Hom.:

313622

Bravo

AF:

0.909

TwinsUK

AF:

0.943

AC:

3497

ALSPAC

AF:

0.937

AC:

3611

ESP6500AA

AF:

0.870

AC:

3264

ESP6500EA

AF:

0.932

AC:

7643

ExAC

AF:

0.907

AC:

109514

Asia WGS

AF:

0.844

AC:

2935

AN:

3478

EpiCase

AF:

0.933

EpiControl

AF:

0.929

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 12, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:2

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.016

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.031

.;T;T;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.37

T;T;T;T

MetaRNN

Benign

9.7e-7

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

L;.;L;.

PhyloP100

-1.6

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.7

N;.;N;N

REVEL

Benign

0.022

Sift

Benign

0.36

T;.;T;T

Sift4G

Benign

0.061

T;T;T;T

Polyphen

0.058

B;.;B;.

Vest4

0.028

MPC

0.053

ClinPred

0.0057

GERP RS

-6.9

Varity_R

0.034

gMVP

0.059

Mutation Taster

=299/1

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