chr14-64070780-A-C

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.10567A>C(p.Lys3523Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,614,150 control chromosomes in the GnomAD database, including 496 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 0.030 ( 119 hom., cov: 33)

Exomes 𝑓: 0.018 ( 377 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.135

Publications

13 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=0.0016273856).

BP6

Variant 14-64070780-A-C is Benign according to our data. Variant chr14-64070780-A-C is described in ClinVar as Benign. ClinVar VariationId is 130456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0675 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.10567A>C	p.Lys3523Gln	missense	Exon 52 of 116	NP_878918.2	Q8WXH0-2
	SYNE2	NM_015180.6		c.10567A>C	p.Lys3523Gln	missense	Exon 52 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.10567A>C	p.Lys3523Gln	missense	Exon 52 of 116	ENSP00000450831.2	Q8WXH0-2
SYNE2	ENST00000344113.8	TSL:1	c.10567A>C	p.Lys3523Gln	missense	Exon 52 of 115	ENSP00000341781.4	Q8WXH0-1
SYNE2	ENST00000358025.7	TSL:5	c.10567A>C	p.Lys3523Gln	missense	Exon 52 of 116	ENSP00000350719.3	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4606

AN:

152178

Hom.:

118

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0535

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.0166

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.0734

Gnomad SAS

AF:

0.00621

Gnomad FIN

AF:

0.0489

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0155

Gnomad OTH

AF:

0.0339

GnomAD2 exomes

AF:

0.0242

AC:

6041

AN:

249522

AF XY:

0.0230

show subpopulations

Gnomad AFR exome

AF:

0.0563

Gnomad AMR exome

AF:

0.0124

Gnomad ASJ exome

AF:

0.00705

Gnomad EAS exome

AF:

0.0824

Gnomad FIN exome

AF:

0.0466

Gnomad NFE exome

AF:

0.0167

Gnomad OTH exome

AF:

0.0205

GnomAD4 exome

AF:

0.0182

AC:

26649

AN:

1461854

Hom.:

377

Cov.:

AF XY:

0.0176

AC XY:

12827

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0564

AC:

1888

AN:

33478

American (AMR)

AF:

0.0139

AC:

621

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00716

AC:

187

AN:

26132

East Asian (EAS)

AF:

0.0600

AC:

2380

AN:

39692

South Asian (SAS)

AF:

0.00425

AC:

367

AN:

86258

European-Finnish (FIN)

AF:

0.0447

AC:

2389

AN:

53418

Middle Eastern (MID)

AF:

0.0128

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0157

AC:

17498

AN:

1111992

Other (OTH)

AF:

0.0206

AC:

1245

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

1524

3048

4571

6095

7619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.0303

AC:

4619

AN:

152296

Hom.:

119

Cov.:

AF XY:

0.0316

AC XY:

2355

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0537

AC:

2232

AN:

41540

American (AMR)

AF:

0.0166

AC:

254

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00922

AC:

AN:

3472

East Asian (EAS)

AF:

0.0736

AC:

382

AN:

5190

South Asian (SAS)

AF:

0.00601

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0489

AC:

519

AN:

10610

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0154

AC:

1051

AN:

68032

Other (OTH)

AF:

0.0331

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

223

447

670

894

1117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0220

Hom.:

102

Bravo

AF:

0.0309

TwinsUK

AF:

0.0156

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.0523

AC:

199

ESP6500EA

AF:

0.0146

AC:

120

ExAC

AF:

0.0243

AC:

2934

Asia WGS

AF:

0.0390

AC:

136

AN:

3478

EpiCase

AF:

0.0203

EpiControl

AF:

0.0202

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Emery-Dreifuss muscular dystrophy 5, autosomal dominant (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.57

CADD

Benign

1.6

(source)

DANN

Benign

0.60

DEOGEN2

Benign

0.0057

Eigen

Benign

-0.97

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0016

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.97

PhyloP100

0.14

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.090

REVEL

Benign

0.022

Sift

Benign

0.62

Sift4G

Benign

0.13

Polyphen

0.010

Vest4

0.18

MPC

0.051

ClinPred

0.00087

GERP RS

0.15

Varity_R

0.034

gMVP

0.096

Mutation Taster

=297/3

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