rs190582637

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.7898A>G(p.Asn2633Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0025 in 1,614,160 control chromosomes in the GnomAD database, including 47 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 0.0020 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 45 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.0320

Publications

4 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=0.003028512).

BP6

Variant 14-64051811-A-G is Benign according to our data. Variant chr14-64051811-A-G is described in ClinVar as [Benign]. Clinvar id is 183364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00205 (312/152314) while in subpopulation SAS AF = 0.0145 (70/4828). AF 95% confidence interval is 0.0118. There are 2 homozygotes in GnomAd4. There are 176 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 312 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.7898A>G	p.Asn2633Ser	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.7898A>G	p.Asn2633Ser	missense_variant	Exon 48 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000289

Gnomad AMI

AF:

0.0187

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0141

Gnomad FIN

AF:

0.00292

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00171

Gnomad OTH

AF:

0.00288

GnomAD2 exomes

AF:

0.00363

AC:

905

AN:

249144

AF XY:

0.00458

show subpopulations

Gnomad AFR exome

AF:

0.000324

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00716

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00255

AC:

3726

AN:

1461846

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2218

AN XY:

727222

show subpopulations

African (AFR)

AF:

0.000269

AC:

AN:

33480

American (AMR)

AF:

0.00134

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00777

AC:

203

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39698

South Asian (SAS)

AF:

0.0163

AC:

1408

AN:

86258

European-Finnish (FIN)

AF:

0.00167

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00151

AC:

1675

AN:

1112004

Other (OTH)

AF:

0.00366

AC:

221

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

260

519

779

1038

1298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00205

AC:

312

AN:

152314

Hom.:

Cov.:

AF XY:

0.00236

AC XY:

176

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41580

American (AMR)

AF:

0.00275

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00519

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.0145

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00292

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00171

AC:

116

AN:

68026

Other (OTH)

AF:

0.00285

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00219

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000519

AC:

ESP6500EA

AF:

0.00229

AC:

ExAC

AF:

0.00364

AC:

440

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.00256

EpiControl

AF:

0.00231

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Aug 07, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Mar 02, 2015

Blueprint Genetics

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:research

- -

Nov 27, 2024

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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 provided

Benign:1

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

0.071

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.17

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.0045

.;T;T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.72

T;T;T;T

MetaRNN

Benign

0.0030

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.46

N;.;N;.

PhyloP100

0.032

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.50

N;.;N;N

REVEL

Benign

0.11

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

0.66

T;T;T;T

Polyphen

0.0010

B;.;B;.

Vest4

0.028

MVP

0.15

MPC

0.041

ClinPred

0.0022

GERP RS

-4.0

Varity_R

0.021

gMVP

0.011

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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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rs190582637

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