NM_182914.3:c.9023T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_182914.3(SYNE2):c.9023T>C(p.Ile3008Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 1,612,470 control chromosomes in the GnomAD database, including 52 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 22 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.961

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
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=0.004129559).

BP6

Variant 14-64052936-T-C is Benign according to our data. Variant chr14-64052936-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 130517.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0109 (1655/152290) while in subpopulation AFR AF = 0.0381 (1584/41550). AF 95% confidence interval is 0.0366. There are 30 homozygotes in GnomAd4. There are 789 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1655 AD,Unknown gene.

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.9023T>C	p.Ile3008Thr	missense	Exon 48 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.9023T>C	p.Ile3008Thr	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.9023T>C	p.Ile3008Thr	missense	Exon 48 of 116	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.9023T>C	p.Ile3008Thr	missense	Exon 48 of 115	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000358025.7	TSL:5	c.9023T>C	p.Ile3008Thr	missense	Exon 48 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0109

AC:

1654

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0382

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00861

GnomAD2 exomes

AF:

0.00286

AC:

708

AN:

247562

AF XY:

0.00218

show subpopulations

Gnomad AFR exome

AF:

0.0412

Gnomad AMR exome

AF:

0.00158

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000115

Gnomad OTH exome

AF:

0.000833

GnomAD4 exome

AF:

0.00112

AC:

1633

AN:

1460180

Hom.:

Cov.:

AF XY:

0.000980

AC XY:

712

AN XY:

726238

show subpopulations

African (AFR)

AF:

0.0401

AC:

1340

AN:

33386

American (AMR)

AF:

0.00178

AC:

AN:

44408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26100

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85490

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000621

AC:

AN:

1111618

Other (OTH)

AF:

0.00224

AC:

135

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

198

298

397

496

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0109

AC:

1655

AN:

152290

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

789

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0381

AC:

1584

AN:

41550

American (AMR)

AF:

0.00301

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68030

Other (OTH)

AF:

0.00852

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

164

247

329

411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00429

Hom.:

Bravo

AF:

0.0131

ESP6500AA

AF:

0.0386

AC:

140

ESP6500EA

AF:

0.000123

AC:

ExAC

AF:

0.00347

AC:

419

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000356

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

not specified (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.53

CADD

Benign

4.3

(source)

DANN

Benign

0.58

DEOGEN2

Benign

0.0031

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0041

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.96

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.2

REVEL

Benign

0.073

Sift

Benign

0.34

Sift4G

Uncertain

0.041

Polyphen

0.63

Vest4

0.12

MVP

0.32

MPC

0.058

ClinPred

0.013

GERP RS

4.5

Varity_R

0.053

gMVP

0.027

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over