rs34843668

Positions:

chr14-64052991-A-T

Variant summary

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

The ENST00000555002.6(SYNE2):c.9078A>T(p.Glu3026Asp) 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 1,610,852 control chromosomes in the GnomAD database, including 889 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 101 hom., cov: 33)

Exomes 𝑓: 0.029 ( 788 hom. )

Consequence

SYNE2
ENST00000555002.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.965

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=0.002384305).

BP6

Variant 14-64052991-A-T is Benign according to our data. Variant chr14-64052991-A-T is described in ClinVar as [Benign]. Clinvar id is 130518.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64052991-A-T is described in Lovd as [Benign]. Variant chr14-64052991-A-T is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0615 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.9078A>T	p.Glu3026Asp	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.9078A>T	p.Glu3026Asp	missense_variant	48/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

4467

AN:

152186

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0649

Gnomad ASJ

AF:

0.0150

Gnomad EAS

AF:

0.0494

Gnomad SAS

AF:

0.0102

Gnomad FIN

AF:

0.0609

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0309

Gnomad OTH

AF:

0.0263

GnomAD3 exomes

AF:

0.0360

AC:

8829

AN:

245360

Hom.:

257

AF XY:

0.0330

AC XY:

4388

AN XY:

133136

show subpopulations

Gnomad AFR exome

AF:

0.00774

Gnomad AMR exome

AF:

0.0858

Gnomad ASJ exome

AF:

0.0142

Gnomad EAS exome

AF:

0.0488

Gnomad SAS exome

AF:

0.0126

Gnomad FIN exome

AF:

0.0520

Gnomad NFE exome

AF:

0.0280

Gnomad OTH exome

AF:

0.0302

GnomAD4 exome

AF:

0.0285

AC:

41577

AN:

1458548

Hom.:

788

Cov.:

AF XY:

0.0279

AC XY:

20214

AN XY:

725274

show subpopulations

Gnomad4 AFR exome

AF:

0.00690

Gnomad4 AMR exome

AF:

0.0834

Gnomad4 ASJ exome

AF:

0.0134

Gnomad4 EAS exome

AF:

0.0524

Gnomad4 SAS exome

AF:

0.0110

Gnomad4 FIN exome

AF:

0.0503

Gnomad4 NFE exome

AF:

0.0270

Gnomad4 OTH exome

AF:

0.0259

GnomAD4 genome

AF:

0.0293

AC:

4466

AN:

152304

Hom.:

101

Cov.:

AF XY:

0.0308

AC XY:

2297

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00762

Gnomad4 AMR

AF:

0.0648

Gnomad4 ASJ

AF:

0.0150

Gnomad4 EAS

AF:

0.0494

Gnomad4 SAS

AF:

0.0102

Gnomad4 FIN

AF:

0.0609

Gnomad4 NFE

AF:

0.0308

Gnomad4 OTH

AF:

0.0260

Alfa

AF:

0.0283

Hom.:

Bravo

AF:

0.0283

TwinsUK

AF:

0.0270

AC:

100

ALSPAC

AF:

0.0259

AC:

100

ESP6500AA

AF:

0.0114

AC:

ESP6500EA

AF:

0.0257

AC:

209

ExAC

AF:

0.0327

AC:

3951

Asia WGS

AF:

0.0300

AC:

104

AN:

3476

EpiCase

AF:

0.0226

EpiControl

AF:

0.0238

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
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:3

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	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Oct 09, 2014	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.031

.;T;T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.83

T;T;T;T

MetaRNN

Benign

0.0024

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;L;.

MutationTaster

Benign

1.0

D;N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-1.7

N;.;N;N

REVEL

Benign

0.059

Sift

Benign

0.030

D;.;D;D

Sift4G

Benign

0.082

T;D;T;D

Polyphen

0.63

P;.;P;.

Vest4

0.15

MutPred

0.094

Loss of ubiquitination at K3027 (P = 0.0642);.;Loss of ubiquitination at K3027 (P = 0.0642);.;

MPC

0.18

ClinPred

0.021

GERP RS

-0.54

Varity_R

0.087

gMVP

0.075

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