rs7161192

Positions:

chr14-64170429-C-A

Variant summary

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

The NM_182914.3(SYNE2):c.17202C>A(p.Leu5734=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,612,700 control chromosomes in the GnomAD database, including 85,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.34 ( 8715 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76842 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.220

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=-0.53).

BP6

Variant 14-64170429-C-A is Benign according to our data. Variant chr14-64170429-C-A is described in ClinVar as [Benign]. Clinvar id is 130485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64170429-C-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.22 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 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.17202C>A	p.Leu5734=	synonymous_variant	94/116	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.17202C>A	p.Leu5734=	synonymous_variant	94/116	1	NM_182914.3	ENSP00000450831	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.335

AC:

50949

AN:

151914

Hom.:

8715

Cov.:

show subpopulations

Gnomad AFR

AF:

0.351

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.376

Gnomad EAS

AF:

0.566

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.313

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.318

GnomAD3 exomes

AF:

0.329

AC:

81919

AN:

249010

Hom.:

14088

AF XY:

0.327

AC XY:

44041

AN XY:

134624

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.260

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.572

Gnomad SAS exome

AF:

0.286

Gnomad FIN exome

AF:

0.328

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.314

GnomAD4 exome

AF:

0.321

AC:

469584

AN:

1460668

Hom.:

76842

Cov.:

AF XY:

0.321

AC XY:

233105

AN XY:

726548

show subpopulations

Gnomad4 AFR exome

AF:

0.353

Gnomad4 AMR exome

AF:

0.266

Gnomad4 ASJ exome

AF:

0.367

Gnomad4 EAS exome

AF:

0.540

Gnomad4 SAS exome

AF:

0.287

Gnomad4 FIN exome

AF:

0.332

Gnomad4 NFE exome

AF:

0.316

Gnomad4 OTH exome

AF:

0.330

GnomAD4 genome

AF:

0.335

AC:

50975

AN:

152032

Hom.:

8715

Cov.:

AF XY:

0.336

AC XY:

24952

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.351

Gnomad4 AMR

AF:

0.291

Gnomad4 ASJ

AF:

0.376

Gnomad4 EAS

AF:

0.567

Gnomad4 SAS

AF:

0.288

Gnomad4 FIN

AF:

0.338

Gnomad4 NFE

AF:

0.320

Gnomad4 OTH

AF:

0.314

Alfa

AF:

0.326

Hom.:

20992

Bravo

AF:

0.336

Asia WGS

AF:

0.371

AC:

1287

AN:

3478

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	Genome-Nilou Lab	Jul 15, 2021	- -
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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.3

DANN

Benign

0.76

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