rs11847087

Positions:

chr14-64053302-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182914.3(SYNE2):c.9389A>G(p.Asn3130Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,608,316 control chromosomes in the GnomAD database, including 2,162 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 585 hom., cov: 33)

Exomes 𝑓: 0.040 ( 1577 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.891

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013741553).

BP6

Variant 14-64053302-A-G is Benign according to our data. Variant chr14-64053302-A-G is described in ClinVar as [Benign]. Clinvar id is 130519.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64053302-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.9389A>G	p.Asn3130Ser	missense_variant	48/116	ENST00000555002.6	NP_878918.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.9389A>G	p.Asn3130Ser	missense_variant	48/116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.0699

AC:

10642

AN:

152158

Hom.:

577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.154

Gnomad AMI

AF:

0.101

Gnomad AMR

AF:

0.0451

Gnomad ASJ

AF:

0.0631

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00828

Gnomad FIN

AF:

0.0267

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0406

Gnomad OTH

AF:

0.0641

GnomAD3 exomes

AF:

0.0404

AC:

9861

AN:

244102

Hom.:

347

AF XY:

0.0381

AC XY:

5035

AN XY:

132230

show subpopulations

Gnomad AFR exome

AF:

0.151

Gnomad AMR exome

AF:

0.0305

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00864

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0423

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0399

AC:

58062

AN:

1456040

Hom.:

1577

Cov.:

AF XY:

0.0389

AC XY:

28155

AN XY:

723852

show subpopulations

Gnomad4 AFR exome

AF:

0.161

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.0613

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00890

Gnomad4 FIN exome

AF:

0.0256

Gnomad4 NFE exome

AF:

0.0401

Gnomad4 OTH exome

AF:

0.0450

GnomAD4 genome

AF:

0.0701

AC:

10673

AN:

152276

Hom.:

585

Cov.:

AF XY:

0.0687

AC XY:

5113

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0450

Gnomad4 ASJ

AF:

0.0631

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00829

Gnomad4 FIN

AF:

0.0267

Gnomad4 NFE

AF:

0.0406

Gnomad4 OTH

AF:

0.0639

Alfa

AF:

0.0478

Hom.:

546

Bravo

AF:

0.0759

TwinsUK

AF:

0.0369

AC:

137

ALSPAC

AF:

0.0420

AC:

162

ESP6500AA

AF:

0.144

AC:

522

ESP6500EA

AF:

0.0406

AC:

330

ExAC

AF:

0.0418

AC:

5043

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.0429

EpiControl

AF:

0.0439

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

SYNE2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 20, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.8

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

.;T;T;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.78

T;T;T;T

MetaRNN

Benign

0.0014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;.

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.4

N;.;N;N

REVEL

Benign

0.031

Sift

Benign

0.21

T;.;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.021

B;.;B;.

Vest4

0.13

MPC

0.043

ClinPred

0.0097

GERP RS

3.0

Varity_R

0.029

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over