rs149391344

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_182914.3(SYNE2):c.11379T>C(p.Leu3793Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00402 in 1,614,176 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0031 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 18 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.290

Publications

1 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=-0.83).

BP6

Variant 14-64081475-T-C is Benign according to our data. Variant chr14-64081475-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 282477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.29 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00313 (476/152296) while in subpopulation NFE AF = 0.00466 (317/68024). AF 95% confidence interval is 0.00424. There are 6 homozygotes in GnomAd4. There are 219 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 476 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.11379T>C	p.Leu3793Leu	synonymous_variant	Exon 57 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.11379T>C	p.Leu3793Leu	synonymous_variant	Exon 57 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.00313

AC:

477

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00691

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00466

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00356

AC:

895

AN:

251464

AF XY:

0.00326

show subpopulations

Gnomad AFR exome

AF:

0.000677

Gnomad AMR exome

AF:

0.00304

Gnomad ASJ exome

AF:

0.00833

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00721

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00619

GnomAD4 exome

AF:

0.00411

AC:

6010

AN:

1461880

Hom.:

Cov.:

AF XY:

0.00404

AC XY:

2939

AN XY:

727236

show subpopulations

African (AFR)

AF:

0.000687

AC:

AN:

33480

American (AMR)

AF:

0.00309

AC:

138

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00754

AC:

197

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.00152

AC:

131

AN:

86258

European-Finnish (FIN)

AF:

0.00786

AC:

420

AN:

53418

Middle Eastern (MID)

AF:

0.00954

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00431

AC:

4790

AN:

1112004

Other (OTH)

AF:

0.00422

AC:

255

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

362

724

1087

1449

1811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.00313

AC:

476

AN:

152296

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41568

American (AMR)

AF:

0.00190

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00691

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00166

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00612

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00466

AC:

317

AN:

68024

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00422

Hom.:

Bravo

AF:

0.00268

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00468

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SYNE2: BP4, BP7, BS2 -

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

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. -

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Aug 17, 2015

Eurofins Ntd Llc (ga)

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

-0.83

CADD

Benign

4.6

(source)

DANN

Benign

0.64

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism

(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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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