rs4027402

Positions:

chr14-64030031-C-T

Variant summary

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

The NM_182914.3(SYNE2):c.6851C>T(p.Ala2284Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.849 in 1,613,584 control chromosomes in the GnomAD database, including 591,320 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 ( 44065 hom., cov: 31)

Exomes 𝑓: 0.86 ( 547255 hom. )

Consequence

SYNE2
NM_182914.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.370

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=1.0792198E-6).

BP6

Variant 14-64030031-C-T is Benign according to our data. Variant chr14-64030031-C-T is described in ClinVar as [Benign]. Clinvar id is 130504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64030031-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.875 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.6851C>T	p.Ala2284Val	missense_variant	44/116	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.6851C>T	p.Ala2284Val	missense_variant	44/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111657

AN:

151870

Hom.:

44065

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.886

Gnomad AMR

AF:

0.789

Gnomad ASJ

AF:

0.794

Gnomad EAS

AF:

0.789

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.865

Gnomad MID

AF:

0.745

Gnomad NFE

AF:

0.881

Gnomad OTH

AF:

0.756

GnomAD3 exomes

AF:

0.818

AC:

203928

AN:

249272

Hom.:

85199

AF XY:

0.825

AC XY:

111604

AN XY:

135246

show subpopulations

Gnomad AFR exome

AF:

0.401

Gnomad AMR exome

AF:

0.827

Gnomad ASJ exome

AF:

0.780

Gnomad EAS exome

AF:

0.780

Gnomad SAS exome

AF:

0.789

Gnomad FIN exome

AF:

0.872

Gnomad NFE exome

AF:

0.879

Gnomad OTH exome

AF:

0.822

GnomAD4 exome

AF:

0.861

AC:

1258443

AN:

1461594

Hom.:

547255

Cov.:

AF XY:

0.860

AC XY:

625284

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.387

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.782

Gnomad4 EAS exome

AF:

0.773

Gnomad4 SAS exome

AF:

0.794

Gnomad4 FIN exome

AF:

0.876

Gnomad4 NFE exome

AF:

0.889

Gnomad4 OTH exome

AF:

0.827

GnomAD4 genome

AF:

0.735

AC:

111674

AN:

151990

Hom.:

44065

Cov.:

AF XY:

0.736

AC XY:

54668

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.790

Gnomad4 ASJ

AF:

0.794

Gnomad4 EAS

AF:

0.789

Gnomad4 SAS

AF:

0.782

Gnomad4 FIN

AF:

0.865

Gnomad4 NFE

AF:

0.881

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.843

Hom.:

111713

Bravo

AF:

0.715

TwinsUK

AF:

0.887

AC:

3290

ALSPAC

AF:

0.880

AC:

3391

ESP6500AA

AF:

0.436

AC:

1605

ESP6500EA

AF:

0.878

AC:

7172

ExAC

AF:

0.812

AC:

98062

Asia WGS

AF:

0.753

AC:

2620

AN:

3478

EpiCase

AF:

0.877

EpiControl

AF:

0.871

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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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	Genome-Nilou Lab	Jul 15, 2021	- -

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

0.11

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.0

DANN

Benign

0.72

DEOGEN2

Benign

0.032

.;T;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.097

LIST_S2

Benign

0.57

T;T;T;T

MetaRNN

Benign

0.0000011

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;.;L;.

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.26

PROVEAN

Benign

-2.0

N;.;N;N

REVEL

Benign

0.036

Sift

Benign

0.19

T;.;T;T

Sift4G

Benign

0.27

T;D;T;D

Polyphen

0.055

B;.;B;.

Vest4

0.079

MPC

0.049

ClinPred

0.0060

GERP RS

1.2

Varity_R

0.026

gMVP

0.16

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