rs8010911

Positions:

chr14-64055956-G-C

Variant summary

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

The ENST00000555002.6(SYNE2):c.9757G>C(p.Asp3253His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.84 in 1,612,456 control chromosomes in the GnomAD database, including 577,480 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43618 hom., cov: 32)

Exomes 𝑓: 0.85 ( 533862 hom. )

Consequence

SYNE2
ENST00000555002.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.89

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=7.1142125E-7).

BP6

Variant 14-64055956-G-C is Benign according to our data. Variant chr14-64055956-G-C is described in ClinVar as [Benign]. Clinvar id is 130520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64055956-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.863 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.9757G>C	p.Asp3253His	missense_variant	49/116	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.9757G>C	p.Asp3253His	missense_variant	49/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.736

AC:

111811

AN:

151994

Hom.:

43614

Cov.:

show subpopulations

Gnomad AFR

AF:

0.450

Gnomad AMI

AF:

0.890

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.753

Gnomad EAS

AF:

0.794

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.857

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.869

Gnomad OTH

AF:

0.757

GnomAD3 exomes

AF:

0.812

AC:

201325

AN:

248000

Hom.:

83171

AF XY:

0.818

AC XY:

110140

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.438

Gnomad AMR exome

AF:

0.821

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.786

Gnomad SAS exome

AF:

0.790

Gnomad FIN exome

AF:

0.864

Gnomad NFE exome

AF:

0.867

Gnomad OTH exome

AF:

0.810

GnomAD4 exome

AF:

0.851

AC:

1243314

AN:

1460344

Hom.:

533862

Cov.:

AF XY:

0.851

AC XY:

617875

AN XY:

726478

show subpopulations

Gnomad4 AFR exome

AF:

0.424

Gnomad4 AMR exome

AF:

0.816

Gnomad4 ASJ exome

AF:

0.743

Gnomad4 EAS exome

AF:

0.778

Gnomad4 SAS exome

AF:

0.796

Gnomad4 FIN exome

AF:

0.867

Gnomad4 NFE exome

AF:

0.876

Gnomad4 OTH exome

AF:

0.820

GnomAD4 genome

AF:

0.735

AC:

111842

AN:

152112

Hom.:

43618

Cov.:

AF XY:

0.737

AC XY:

54784

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.449

Gnomad4 AMR

AF:

0.780

Gnomad4 ASJ

AF:

0.753

Gnomad4 EAS

AF:

0.794

Gnomad4 SAS

AF:

0.782

Gnomad4 FIN

AF:

0.857

Gnomad4 NFE

AF:

0.869

Gnomad4 OTH

AF:

0.754

Alfa

AF:

0.819

Hom.:

16804

Bravo

AF:

0.718

TwinsUK

AF:

0.879

AC:

3259

ALSPAC

AF:

0.871

AC:

3355

ESP6500AA

AF:

0.474

AC:

1821

ESP6500EA

AF:

0.864

AC:

7124

ExAC

AF:

0.806

AC:

97406

Asia WGS

AF:

0.758

AC:

2637

AN:

3478

EpiCase

AF:

0.868

EpiControl

AF:

0.861

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Dec 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 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	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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	Genome-Nilou Lab	Jul 15, 2021	- -

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

0.15

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.036

.;T;T;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.85

T;T;T;T

MetaRNN

Benign

7.1e-7

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

M;.;M;.

MutationTaster

Benign

0.99

P;P;P;P

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.8

N;.;N;N

REVEL

Benign

0.076

Sift

Benign

0.11

T;.;T;T

Sift4G

Uncertain

0.0040

D;D;D;D

Polyphen

0.34

B;.;B;.

Vest4

0.25

MPC

0.26

ClinPred

0.031

GERP RS

2.9

Varity_R

0.048

gMVP

0.18

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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