rs4902264

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_182914.3(SYNE2):c.5906T>C(p.Met1969Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.848 in 1,613,774 control chromosomes in the GnomAD database, including 589,138 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 0.73 ( 43964 hom., cov: 32)

Exomes 𝑓: 0.86 ( 545174 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0370

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=7.5595824E-7).

BP6

Variant 14-64024977-T-C is Benign according to our data. Variant chr14-64024977-T-C is described in ClinVar as [Benign]. Clinvar id is 130501.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64024977-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.873 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SYNE2	NM_182914.3 link	c.5906T>C	p.Met1969Thr	missense_variant	Exon 40 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.5906T>C	p.Met1969Thr	missense_variant	Exon 40 of 116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.734

AC:

111623

AN:

152004

Hom.:

43963

Cov.:

show subpopulations

Gnomad AFR

AF:

0.423

Gnomad AMI

AF:

0.884

Gnomad AMR

AF:

0.776

Gnomad ASJ

AF:

0.791

Gnomad EAS

AF:

0.792

Gnomad SAS

AF:

0.803

Gnomad FIN

AF:

0.865

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.879

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.816

AC:

203604

AN:

249398

Hom.:

84839

AF XY:

0.825

AC XY:

111622

AN XY:

135318

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.803

Gnomad ASJ exome

AF:

0.774

Gnomad EAS exome

AF:

0.788

Gnomad SAS exome

AF:

0.810

Gnomad FIN exome

AF:

0.873

Gnomad NFE exome

AF:

0.876

Gnomad OTH exome

AF:

0.815

GnomAD4 exome

AF:

0.860

AC:

1256367

AN:

1461654

Hom.:

545174

Cov.:

AF XY:

0.859

AC XY:

624734

AN XY:

727128

show subpopulations

Gnomad4 AFR exome

AF:

0.391

Gnomad4 AMR exome

AF:

0.799

Gnomad4 ASJ exome

AF:

0.777

Gnomad4 EAS exome

AF:

0.777

Gnomad4 SAS exome

AF:

0.813

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.886

Gnomad4 OTH exome

AF:

0.826

GnomAD4 genome

AF:

0.734

AC:

111639

AN:

152120

Hom.:

43964

Cov.:

AF XY:

0.735

AC XY:

54638

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.423

Gnomad4 AMR

AF:

0.776

Gnomad4 ASJ

AF:

0.791

Gnomad4 EAS

AF:

0.792

Gnomad4 SAS

AF:

0.804

Gnomad4 FIN

AF:

0.865

Gnomad4 NFE

AF:

0.879

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.843

Hom.:

136607

Bravo

AF:

0.712

TwinsUK

AF:

0.883

AC:

3275

ALSPAC

AF:

0.878

AC:

3383

ESP6500AA

AF:

0.444

AC:

1642

ESP6500EA

AF:

0.875

AC:

7155

ExAC

AF:

0.811

AC:

98029

Asia WGS

AF:

0.763

AC:

2655

AN:

3478

EpiCase

AF:

0.875

EpiControl

AF:

0.867

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 14, 2018

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:3

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.014

.;T;T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.44

T;T;T;T

MetaRNN

Benign

7.6e-7

T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.69

N;.;N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

1.1

N;.;N;N

REVEL

Benign

0.035

Sift

Benign

1.0

T;.;T;T

Sift4G

Benign

0.091

T;D;T;D

Polyphen

0.0030

B;.;B;.

Vest4

0.13

MPC

0.053

ClinPred

0.0035

GERP RS

-1.3

Varity_R

0.035

gMVP

0.077

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