14-64219407-G-T

Position:

chr14-64219407-G-T

Variant summary

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

The NM_182914.3(SYNE2):c.19857G>T(p.Leu6619Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,613,108 control chromosomes in the GnomAD database, including 58,800 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 4771 hom., cov: 31)

Exomes 𝑓: 0.27 ( 54029 hom. )

Consequence

SYNE2
NM_182914.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.932

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:

SYNE2 (HGNC:):

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=-0.52).

BP6

Variant 14-64219407-G-T is Benign according to our data. Variant chr14-64219407-G-T is described in ClinVar as [Benign]. Clinvar id is 130490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-64219407-G-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.932 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.277 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.19857G>T	p.Leu6619Leu	synonymous_variant	110/116	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.19857G>T	p.Leu6619Leu	synonymous_variant	110/116	1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.245

AC:

37223

AN:

151888

Hom.:

4775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.211

Gnomad AMI

AF:

0.412

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.254

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.262

GnomAD3 exomes

AF:

0.236

AC:

59290

AN:

250938

Hom.:

7579

AF XY:

0.243

AC XY:

33021

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.208

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.0964

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.281

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.267

AC:

390347

AN:

1461102

Hom.:

54029

Cov.:

AF XY:

0.267

AC XY:

194226

AN XY:

726894

show subpopulations

Gnomad4 AFR exome

AF:

0.207

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.331

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.255

Gnomad4 FIN exome

AF:

0.229

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.264

GnomAD4 genome

AF:

0.245

AC:

37228

AN:

152006

Hom.:

4771

Cov.:

AF XY:

0.240

AC XY:

17838

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.211

Gnomad4 AMR

AF:

0.205

Gnomad4 ASJ

AF:

0.331

Gnomad4 EAS

AF:

0.110

Gnomad4 SAS

AF:

0.254

Gnomad4 FIN

AF:

0.221

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.259

Alfa

AF:

0.264

Hom.:

3928

Bravo

AF:

0.240

Asia WGS

AF:

0.199

AC:

695

AN:

3478

EpiCase

AF:

0.288

EpiControl

AF:

0.291

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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
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. -

not provided

Benign:2

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

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

-0.52

CADD

Benign

0.60

DANN

Benign

0.57

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