Variant rs190518140 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000555002.6(SYNE2):c.10510A>G(p.Thr3504Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000496 in 1,614,178 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

SYNE2
ENST00000555002.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.72

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=0.00614202).

BP6

Variant 14-64070723-A-G is Benign according to our data. Variant chr14-64070723-A-G is described in ClinVar as [Benign]. Clinvar id is 470911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64070723-A-G is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00264 (402/152340) while in subpopulation AFR AF= 0.00895 (372/41576). AF 95% confidence interval is 0.0082. There are 1 homozygotes in gnomad4. There are 188 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 402 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.10510A>G	p.Thr3504Ala	missense_variant	52/116	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.10510A>G	p.Thr3504Ala	missense_variant	52/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.00263

AC:

400

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000653

AC:

163

AN:

249512

Hom.:

AF XY:

0.000569

AC XY:

AN XY:

135372

show subpopulations

Gnomad AFR exome

AF:

0.00930

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000272

AC:

398

AN:

1461838

Hom.:

Cov.:

AF XY:

0.000226

AC XY:

164

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00956

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.000695

GnomAD4 genome

AF:

0.00264

AC:

402

AN:

152340

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

188

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.00895

Gnomad4 AMR

AF:

0.00183

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000596

Hom.:

Bravo

AF:

0.00323

ESP6500AA

AF:

0.00947

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000911

AC:

110

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.027

.;T;T;T;T

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.60

T;T;T;T;T

MetaRNN

Benign

0.0061

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.;M;.;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

N;.;N;N;N

REVEL

Benign

0.070

Sift

Benign

0.048

D;.;T;D;T

Sift4G

Benign

0.10

T;T;T;T;T

Polyphen

0.57

P;.;B;.;.

Vest4

0.35

MVP

0.30

MPC

0.19

ClinPred

0.016

GERP RS

4.3

Varity_R

0.053

gMVP

0.10

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