chr14-64190137-T-C

Position:

chr14-64190137-T-C

Variant summary

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

The NM_182914.3(SYNE2):c.17938T>C(p.Leu5980=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 1,613,720 control chromosomes in the GnomAD database, including 119,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18869 hom., cov: 31)

Exomes 𝑓: 0.36 ( 100930 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.100

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=-0.57).

BP6

Variant 14-64190137-T-C is Benign according to our data. Variant chr14-64190137-T-C is described in ClinVar as [Benign]. Clinvar id is 130488.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64190137-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 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.17938T>C	p.Leu5980=	synonymous_variant	99/116	ENST00000555002.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SYNE2	ENST00000555002.6 linkuse as main transcript	c.17938T>C	p.Leu5980=	synonymous_variant	99/116	1	NM_182914.3	P4	Q8WXH0-2

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70641

AN:

151804

Hom.:

18831

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.375

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.494

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.396

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.354

Gnomad OTH

AF:

0.463

GnomAD3 exomes

AF:

0.388

AC:

97453

AN:

251396

Hom.:

20423

AF XY:

0.382

AC XY:

51923

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.357

Gnomad ASJ exome

AF:

0.492

Gnomad EAS exome

AF:

0.383

Gnomad SAS exome

AF:

0.392

Gnomad FIN exome

AF:

0.286

Gnomad NFE exome

AF:

0.355

Gnomad OTH exome

AF:

0.371

GnomAD4 exome

AF:

0.364

AC:

531648

AN:

1461796

Hom.:

100930

Cov.:

AF XY:

0.364

AC XY:

264385

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.758

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.491

Gnomad4 EAS exome

AF:

0.356

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.284

Gnomad4 NFE exome

AF:

0.349

Gnomad4 OTH exome

AF:

0.391

GnomAD4 genome

AF:

0.466

AC:

70728

AN:

151924

Hom.:

18869

Cov.:

AF XY:

0.458

AC XY:

34003

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.388

Gnomad4 ASJ

AF:

0.494

Gnomad4 EAS

AF:

0.369

Gnomad4 SAS

AF:

0.396

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.354

Gnomad4 OTH

AF:

0.457

Alfa

AF:

0.388

Hom.:

28018

Bravo

AF:

0.487

Asia WGS

AF:

0.384

AC:

1334

AN:

3478

EpiCase

AF:

0.369

EpiControl

AF:

0.376

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:4

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	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 28, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 09, 2018	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.30

DANN

Benign

0.53

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