Variant 14-64221457-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_182914.3(SYNE2):c.20062-119G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 1,588,304 control chromosomes in the GnomAD database, including 265,110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34069 hom., cov: 32)

Exomes 𝑓: 0.56 ( 231041 hom. )

Consequence

SYNE2
NM_182914.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.686

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 14-64221457-G-C is Benign according to our data. Variant chr14-64221457-G-C is described in ClinVar as [Benign]. Clinvar id is 281196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.87 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.20062-119G>C		intron_variant		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.20062-119G>C		intron_variant		1	NM_182914.3	ENSP00000450831.2		Q8WXH0-2A0A0C4DGK3

Frequencies

GnomAD3 genomes

AF:

0.654

AC:

99328

AN:

151980

Hom.:

34017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.877

Gnomad AMI

AF:

0.781

Gnomad AMR

AF:

0.558

Gnomad ASJ

AF:

0.641

Gnomad EAS

AF:

0.701

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.577

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.632

GnomAD4 exome

AF:

0.563

AC:

809068

AN:

1436206

Hom.:

231041

AF XY:

0.560

AC XY:

400253

AN XY:

714314

show subpopulations

Gnomad4 AFR exome

AF:

0.890

Gnomad4 AMR exome

AF:

0.531

Gnomad4 ASJ exome

AF:

0.641

Gnomad4 EAS exome

AF:

0.650

Gnomad4 SAS exome

AF:

0.498

Gnomad4 FIN exome

AF:

0.566

Gnomad4 NFE exome

AF:

0.553

Gnomad4 OTH exome

AF:

0.589

GnomAD4 genome

AF:

0.654

AC:

99434

AN:

152098

Hom.:

34069

Cov.:

AF XY:

0.650

AC XY:

48311

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.877

Gnomad4 AMR

AF:

0.558

Gnomad4 ASJ

AF:

0.641

Gnomad4 EAS

AF:

0.701

Gnomad4 SAS

AF:

0.500

Gnomad4 FIN

AF:

0.577

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.631

Alfa

AF:

0.605

Hom.:

3445

Bravo

AF:

0.666

Asia WGS

AF:

0.612

AC:

2127

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	This variant is associated with the following publications: (PMID: 16118344) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Sep 04, 2015

- -

Emery-Dreifuss muscular dystrophy 5, autosomal dominant

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

2.4

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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