chr14-64087799-A-G

Position:

chr14-64087799-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_182914.3(SYNE2):c.11613A>G(p.Val3871=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0762 in 1,613,930 control chromosomes in the GnomAD database, including 5,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 992 hom., cov: 32)

Exomes 𝑓: 0.073 ( 4373 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.543

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:

ESR2 (HGNC:3468): (estrogen receptor 2) This gene encodes a member of the family of estrogen receptors and superfamily of nuclear receptor transcription factors. The gene product contains an N-terminal DNA binding domain and C-terminal ligand binding domain and is localized to the nucleus, cytoplasm, and mitochondria. Upon binding to 17beta-estradiol or related ligands, the encoded protein forms homo- or hetero-dimers that interact with specific DNA sequences to activate transcription. Some isoforms dominantly inhibit the activity of other estrogen receptor family members. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some of these variants has not been fully characterized. [provided by RefSeq, Jul 2008]

ESR2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 14-64087799-A-G is Benign according to our data. Variant chr14-64087799-A-G is described in ClinVar as [Benign]. Clinvar id is 130459.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64087799-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.543 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SYNE2	NM_182914.3 linkuse as main transcript	c.11613A>G	p.Val3871=	synonymous_variant	58/116	ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.11613A>G	p.Val3871=	synonymous_variant	58/116	1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15941

AN:

152154

Hom.:

984

Cov.:

show subpopulations

Gnomad AFR

AF:

0.171

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0844

Gnomad EAS

AF:

0.0504

Gnomad SAS

AF:

0.0617

Gnomad FIN

AF:

0.0869

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.0741

Gnomad OTH

AF:

0.0973

GnomAD3 exomes

AF:

0.0832

AC:

20879

AN:

250920

Hom.:

1028

AF XY:

0.0798

AC XY:

10831

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.168

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.0846

Gnomad EAS exome

AF:

0.0492

Gnomad SAS exome

AF:

0.0607

Gnomad FIN exome

AF:

0.0798

Gnomad NFE exome

AF:

0.0728

Gnomad OTH exome

AF:

0.0866

GnomAD4 exome

AF:

0.0732

AC:

106938

AN:

1461658

Hom.:

4373

Cov.:

AF XY:

0.0726

AC XY:

52813

AN XY:

727118

show subpopulations

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.0794

Gnomad4 EAS exome

AF:

0.0529

Gnomad4 SAS exome

AF:

0.0595

Gnomad4 FIN exome

AF:

0.0759

Gnomad4 NFE exome

AF:

0.0693

Gnomad4 OTH exome

AF:

0.0781

GnomAD4 genome

AF:

0.105

AC:

15997

AN:

152272

Hom.:

992

Cov.:

AF XY:

0.105

AC XY:

7838

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.172

Gnomad4 AMR

AF:

0.112

Gnomad4 ASJ

AF:

0.0844

Gnomad4 EAS

AF:

0.0503

Gnomad4 SAS

AF:

0.0619

Gnomad4 FIN

AF:

0.0869

Gnomad4 NFE

AF:

0.0741

Gnomad4 OTH

AF:

0.0991

Alfa

AF:

0.0798

Hom.:

1055

Bravo

AF:

0.109

Asia WGS

AF:

0.0860

AC:

298

AN:

3478

EpiCase

AF:

0.0684

EpiControl

AF:

0.0717

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:2

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	Invitae	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 15, 2013

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

SYNE2-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.9

DANN

Benign

0.67

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