rs4027405

Positions:

chr14-64031319-G-A

Variant summary

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

The NM_182914.3(SYNE2):c.7183G>A(p.Ala2395Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 1,613,968 control chromosomes in the GnomAD database, including 672,553 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.88 ( 58781 hom., cov: 32)

Exomes 𝑓: 0.92 ( 613772 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.85

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=9.149704E-7).

BP6

Variant 14-64031319-G-A is Benign according to our data. Variant chr14-64031319-G-A is described in ClinVar as [Benign]. Clinvar id is 130511.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64031319-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.92 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.7183G>A	p.Ala2395Thr	missense_variant	45/116	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.7183G>A	p.Ala2395Thr	missense_variant	45/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.876

AC:

133309

AN:

152112

Hom.:

58734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.780

Gnomad AMI

AF:

0.924

Gnomad AMR

AF:

0.906

Gnomad ASJ

AF:

0.845

Gnomad EAS

AF:

0.857

Gnomad SAS

AF:

0.840

Gnomad FIN

AF:

0.927

Gnomad MID

AF:

0.839

Gnomad NFE

AF:

0.926

Gnomad OTH

AF:

0.878

GnomAD3 exomes

AF:

0.895

AC:

222525

AN:

248624

Hom.:

99935

AF XY:

0.894

AC XY:

120761

AN XY:

135022

show subpopulations

Gnomad AFR exome

AF:

0.773

Gnomad AMR exome

AF:

0.942

Gnomad ASJ exome

AF:

0.829

Gnomad EAS exome

AF:

0.842

Gnomad SAS exome

AF:

0.847

Gnomad FIN exome

AF:

0.924

Gnomad NFE exome

AF:

0.920

Gnomad OTH exome

AF:

0.881

GnomAD4 exome

AF:

0.916

AC:

1338252

AN:

1461738

Hom.:

613772

Cov.:

AF XY:

0.913

AC XY:

664192

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.765

Gnomad4 AMR exome

AF:

0.938

Gnomad4 ASJ exome

AF:

0.829

Gnomad4 EAS exome

AF:

0.868

Gnomad4 SAS exome

AF:

0.850

Gnomad4 FIN exome

AF:

0.927

Gnomad4 NFE exome

AF:

0.929

Gnomad4 OTH exome

AF:

0.895

GnomAD4 genome

AF:

0.876

AC:

133409

AN:

152230

Hom.:

58781

Cov.:

AF XY:

0.875

AC XY:

65131

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.780

Gnomad4 AMR

AF:

0.906

Gnomad4 ASJ

AF:

0.845

Gnomad4 EAS

AF:

0.857

Gnomad4 SAS

AF:

0.840

Gnomad4 FIN

AF:

0.927

Gnomad4 NFE

AF:

0.926

Gnomad4 OTH

AF:

0.879

Alfa

AF:

0.908

Hom.:

154635

Bravo

AF:

0.870

TwinsUK

AF:

0.932

AC:

3457

ALSPAC

AF:

0.923

AC:

3557

ESP6500AA

AF:

0.782

AC:

3013

ESP6500EA

AF:

0.923

AC:

7631

ExAC

AF:

0.892

AC:

107745

Asia WGS

AF:

0.850

AC:

2956

AN:

3478

EpiCase

AF:

0.917

EpiControl

AF:

0.912

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
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	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.0098

.;T;T;T

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.75

T;T;T;T

MetaRNN

Benign

9.1e-7

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.1

L;.;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.52

N;.;N;N

REVEL

Benign

0.057

Sift

Benign

0.25

T;.;T;T

Sift4G

Benign

0.32

T;T;T;T

Polyphen

0.0090

B;.;B;.

Vest4

0.025

MPC

0.25

ClinPred

0.013

GERP RS

3.2

Varity_R

0.025

gMVP

0.12

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