rs11628107

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.7690A>G(p.Ile2564Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 1,613,676 control chromosomes in the GnomAD database, including 893 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 (★★).

Frequency

Genomes: 𝑓 0.029 ( 99 hom., cov: 32)

Exomes 𝑓: 0.029 ( 794 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.0980

Publications

15 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
left ventricular noncompaction
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Emery-Dreifuss muscular dystrophy 5, autosomal dominant
Inheritance: Unknown, AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Illumina, 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=0.002633661).

BP6

Variant 14-64051603-A-G is Benign according to our data. Variant chr14-64051603-A-G is described in ClinVar as Benign. ClinVar VariationId is 130512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182914.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SYNE2	NM_182914.3	MANE Select	c.7690A>G	p.Ile2564Val	missense	Exon 48 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.7690A>G	p.Ile2564Val	missense	Exon 48 of 115	NP_055995.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SYNE2	ENST00000555002.6	TSL:1 MANE Select	c.7690A>G	p.Ile2564Val	missense	Exon 48 of 116	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.7690A>G	p.Ile2564Val	missense	Exon 48 of 115	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000358025.7	TSL:5	c.7690A>G	p.Ile2564Val	missense	Exon 48 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4460

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0646

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0496

Gnomad SAS

AF:

0.00994

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0263

GnomAD2 exomes

AF:

0.0359

AC:

8930

AN:

248864

AF XY:

0.0328

show subpopulations

Gnomad AFR exome

AF:

0.00777

Gnomad AMR exome

AF:

0.0853

Gnomad ASJ exome

AF:

0.0140

Gnomad EAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0519

Gnomad NFE exome

AF:

0.0281

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0285

AC:

41664

AN:

1461356

Hom.:

794

Cov.:

AF XY:

0.0279

AC XY:

20270

AN XY:

727018

show subpopulations

African (AFR)

AF:

0.00695

AC:

232

AN:

33386

American (AMR)

AF:

0.0833

AC:

3714

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.0133

AC:

348

AN:

26128

East Asian (EAS)

AF:

0.0526

AC:

2088

AN:

39690

South Asian (SAS)

AF:

0.0110

AC:

951

AN:

86198

European-Finnish (FIN)

AF:

0.0503

AC:

2685

AN:

53404

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0270

AC:

30058

AN:

1111838

Other (OTH)

AF:

0.0259

AC:

1565

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

2162

4324

6485

8647

10809

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1126

2252

3378

4504

5630

<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:

0.0293

AC:

4459

AN:

152320

Hom.:

Cov.:

AF XY:

0.0307

AC XY:

2288

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.00762

AC:

317

AN:

41576

American (AMR)

AF:

0.0646

AC:

989

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0150

AC:

AN:

3468

East Asian (EAS)

AF:

0.0495

AC:

257

AN:

5190

South Asian (SAS)

AF:

0.00995

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0603

AC:

640

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0309

AC:

2100

AN:

68028

Other (OTH)

AF:

0.0260

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

221

442

664

885

1106

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0286

Hom.:

319

Bravo

AF:

0.0283

TwinsUK

AF:

0.0275

AC:

102

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.0112

AC:

ESP6500EA

AF:

0.0280

AC:

228

ExAC

AF:

0.0328

AC:

3968

Asia WGS

AF:

0.0300

AC:

103

AN:

3478

EpiCase

AF:

0.0226

EpiControl

AF:

0.0239

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Emery-Dreifuss muscular dystrophy 5, autosomal dominant (3)

not provided (3)

not specified (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.79

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.0077

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.71

MetaRNN

Benign

0.0026

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

0.098

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.24

REVEL

Benign

0.067

Sift

Benign

1.0

Sift4G

Benign

0.29

Polyphen

0.012

Vest4

0.11

MPC

0.045

ClinPred

0.0018

GERP RS

4.0

Varity_R

0.017

gMVP

0.018

Mutation Taster

=286/14

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over